- PMID
- Gene Name
- Molecular Event
- Function in UC
- 20057336
- UGT1A1
- mutation
- Pathogenesis
- Method
- c.-3279T>G, c.-3156G>A, and A(TA)7TAA
- Summary
- ADD A NOTE
- G, in the UGT1A1 promoter is a risk factor for neonatal jaundice in the Malay population. Pediatric research, 2010 Apr [Go to PubMed]
- The uridine diphosphoglucuronate-glucuronosyltransferase 1A1 (UGT1A1) gene encodes the enzyme responsible for bilirubin glucuronidation. To evaluate the contribution of UGT1A1 promoter mutations to neonatal jaundice, we determined the genotypes of c.-3279T>G, c.-3156G>A, and A(TA)7TAA in Malay infants with neonatal jaundice (patients) and in infants without neonatal jaundice (controls). In our population study, only c.-3279T>G was associated with neonatal jaundice. The genotype distributions between both groups were significantly different (p = 0.003): the frequency of homozygosity for c.-3279G was much higher in patients than those in controls. Allele frequency of c.-3279G was significantly higher in patients than those in controls (p = 0.006). We then investigated changes in transcriptional activity because of c.-3279T>G. Luciferase reporter assay in HepG2 cells demonstrated that transcriptional activity of the c.-3279G allele was significantly lower than that of the c.-3279T allele in both the absence and presence of bilirubin. Luciferase reporter assay in COS-7 cells elucidated that c.-3279T>G modified the synergistic effects of the nuclear factors associated with transcriptional machinery. In conclusion, the c.-3279T>G mutation in the UGT1A1 promoter is a genetic risk factor for neonatal jaundice.
- 12680285
- UGT1A1
- mutation
- Diagnosis
- Method
- A(TA)nTAA region in the promoter.
- Summary
- The aim of this work was to evaluate the influence of abnormal UDP-glucoronosyltransferase-1 (UGT1A1) gene variant, on the incidence and severity of Neonatal hyperbilirubinemia, in glucose-6-phosphate dehydrogenase (G6PD) deficient newborns.
- [Glucose-6-phosphate dehydrogenase deficiency, neonatal hyperbilirubinemia and Gilbert syndrome]. Acta médica portuguesa, [Go to PubMed]
- The aim of this work was to evaluate the influence of abnormal UDP-glucoronosyltransferase-1 (UGT1A1) gene variant, on the incidence and severity of neonatal hyperbilirubinemia, in glucose-6-phosphate dehydrogenase (G6PD) deficient newborns. The A(TA)nTAA region in the promoter of the UGT1A1 gene was analysed in 20 children with G6PD deficiency. Fourteen of these children had the African type variant (G6PDA-) and 6 had different variants (G6PDNara, G6PDGuadalajara, G6PDDurham, G6PDTomah, G6PDAveiro e G6PDNashville) related to chronic nonspherocytic haemolytic anaemia (CNSHA). The existence of a positive history of neonatal hyperbilirubinemia, as well as its severity was registered. The incidence of neonatal hyperbilirubinemia was increased in this group of children (90%) and was not associated with abnormal alleles of the UGT1A1 gene. It was not possible to assess the influence of abnormal alleles in the severity of the neonatal hyperbilirubinemia. However, these abnormal alleles did not account for the seveity of jaundice in children who presented variants related to CNSHA, since 5 were treated with an exchange transfusion and none presented abnormal alleles.
- 12502904
- UGT1A1
- mutation
- Diagnosis; Pathogenesis
- Method
- glycine to arginine at codon 71 (G71R), in the cod
- Summary
- This finding strongly suggests that the presence of the G71R mutation contributes to the development of Neonatal hyperbilirubinemia in the Japanese population
- Gly71Arg mutation of the bilirubin UDP-glucuronosyltransferase 1A1 gene is associated with neonatal hyperbilirubinemia in the Japanese population. The Kobe journal of medical sciences, 2002 Aug [Go to PubMed]
- The serum bilirubin level of Japanese newborn infants in their first few days is significantly higher than that in Caucasian newborn infants, suggesting that there might be genetic risk factors for the development of neonatal hyperbilirubinemia in the Japanese population. Recently, it has been reported that a variant TATA box in the promoter region of the bilirubin UDP-glucuronosyltransferase 1 (UGT1A1) gene is associated with the development of neonatal hyperbilirubinemia. This finding led us to the idea that a mutation, glycine to arginine at codon 71 (G71R), in the coding region of the UGT1A1 gene can cause neonatal hyperbilirubinemia. In this study, we determined the genotypic distribution of the G71R mutation in 72 Japanese newborn infants: 23 infants with hyperbilirubinemia and 49 infants without hyperbilirubinemia. In the hyperbilirubinemia group, 15 of 23 newborn infants had the G71R mutation (3 homozygotes and 12 heterozygotes), whereas in the non-hyperbilirubinemia group 16 of 49 newborn infants ha the G71R mutation (1 homozygote and 15 heterozygotes). Therefore, the G71R mutation was present significantly more frequently in the hyperbilirubinemia group than in the non-hyperbilirubinemia group. This finding strongly suggests that the presence of the G71R mutation contributes to the development of neonatal hyperbilirubinemia in the Japanese population.
- 20528217
- UGT1A1
- mutation
- Diagnosis
- Method
- UGT1A1 gene, glycine to arginine at codon 71 (G71R
- Summary
- The difference between the groups was not statistically significant. Our results suggest that G71R mutation of UGT1A1 is not rare; however, an association between G71R mutation and hyperbilirubinemia of unexplained cause has not been shown in Turkish newborns.
- Neonatal hyperbilirubinemia and G71R mutation of the UGT1A1 gene in Turkish patients. neonatal medicine : the official journal of the E, 2011 Feb [Go to PubMed]
- Nonphysiologic hyperbilirubinemia of unexplained cause is prevalent among Turkish newborns, suggesting that there might be genetic risk factors in this population. Mutation of the UGT1A1 gene, glycine to arginine at codon 71 (G71R), is related to the development of neonatal jaundice in East Asian populations but the frequency of this mutation is rare among Caucasian populations. There are insufficient data on the G71R mutation in Turkish newborns with hyperbilirubinemia. The aim of this study was to investigate the genotypic distribution of the G71R mutation and its relationship with nonphysiologic hyperbilirubinemia of unexplained cause in Turkish newborns.
Polymerase chain reaction, restriction fragment length polymorphism and agarose gel electrophoresis techniques were used for detection of G71R mutation in 109 newborn infants: 39 with hyperbilirubinemia and 70 without hyperbilirubinemia.
The genotypic distribution for the mutation was 70 G/G, 32 A/G, 7 A/A genotypes and the mutated allele frequency was 0.22. The frequency of G71R mutation was 33.3 % (n = 13) A/G, 7.7% (n = 3) A/A in the hyperbilirubinemia group and 27.1% (n = 19) A/R, 5% (n = 4) A/A in the nonhyperbilirubinemia group. The difference between the groups was not statistically significant.
Our results suggest that G71R mutation of UGT1A1 is not rare; however, an association between G71R mutation and hyperbilirubinemia of unexplained cause has not been shown in Turkish newborns. - 17166930
- UGT1A1
- mutation
- Pathogenesis
- Method
- promoter region [thymine-adenine(TA)]7 Polymorphis
- Summary
- it is concluded that UGT1A1 promoter region Polymorphism was not a risk factor for Neonatal jaundice.
- The frequency of UDP-glucuronosyltransferase 1A1 promoter region (TA)7 polymorphism in newborns and it's relation with jaundice. Journal of tropical pediatrics, 2007 Feb [Go to PubMed]
- Increased bilirubin formation and decreased bilirubin conjugation play an important role in the pathogenesis of the newborn jaundice. Although physiologic jaundice is seen in most of the newborns, there are many risk factors that affect the severity and duration of hyperbilirubinemia. The latest studies showed that the frequency and severity of neonatal jaundice have been increased when mutations of the gene coding UDP-glucuronosyltransferase(UGT)1A1 coexist with other risk factors. Healthy term newborns weighing over 2500 g. were included in this study. The patient group consisted of 107 newborns either with total bilirubin level over 15 mg dl(-1) within 7 days or 5 mg dl(-1) after 15 days of age. The control group consisted of 55 newborns with bilirubin levels in physiological ranges. We investigated the frequency of promoter region [thymine-adenine(TA)]7 polymorphism in UGT1A1 gene. Factors which might cause pathologic and prolonged jaundice with coexisting polymorphism were also investigated. UGT1A1 6/7 enotype was found to be 11% in patient group and 13% in the control group. The difference between patient and control groups was not statistically significant. (TA)7 allele frequency was 0.069 and it is concluded that UGT1A1 promoter region polymorphism was not a risk factor for neonatal jaundice.
- 12105841
- UGT1A1
- mutation
- Diagnosis
- Method
- the A(TA)7TAA promoter variant
- Summary
- The results indicate that carriage of the homozygous 211 G to A variation within the coding region in the UGT1A1 gene is an additive risk factor for Neonatal hyperbilirubinemia in G6PD-deficient Taiwanese male neonates.
- Glucose-6-phosphate dehydrogenase deficiency, the UDP-glucuronosyl transferase 1A1 gene, and neonatal hyperbilirubinemia. Gastroenterology, 2002 Jul [Go to PubMed]
- Coinheritance of the A(TA)7TAA promoter variant in the uridine 5'-diphosphate-glucuronosyl transferase 1A1 (UGT1A1) gene and glucose-6-phosphate dehydrogenase (G6PD) deficiency is crucial to hyperbilirubinemia in white male neonates. A variation rate of 29.3% was determined within the coding region of the UGT1A1 gene in Taiwanese subjects, suggesting the hypothesis that this variation may influence incidence of hyperbilirubinemia in male neonates with G6PD deficiency.
The full sequence of the UGT1A1 gene was identified for 212 G6PD-deficient and 232 control male neonates by using polymerase chain reaction (PCR).
Both study and control groups were divided into 5 subgroups according to their UGT1A1 genotypes. Most subjects carried G to A variation at nucleotide 211 for both genotypes of heterozygous variation within coding region and homozygous variation. No significant differences were noted for the frequencies of the 5 UGT1A1 genotypes, gestation age, and birth weight comparing the G6PD-deficient and control groups. The incidence of hyperbilirubinemia, however, was significantly higher for the study group than for the controls. This difference was noted only for the subgroup bearing the homozygous variant of the UGT1A1 gene. In the subgroup of homozygous variation, the serum bilirubin value was significantly higher for G6PD-deficient neonates than for controls. All 11 G6PD-deficient neonates with the homozygous 211 G to A variation suffered from hyperbilirubinemia.
The results indicate that carriage of the homozygous 211 G to A variation within the coding region in the UGT1A1 gene is an additive risk factor for neonatal hyperbilirubinemia in G6PD-deficient Taiwanese male neonates. - 17888052
- UGT1A1
- mutation
- Diagnosis; Pathogenesis
- Method
- exon 1 of UGT1A1 gene
- Summary
- The UGT1A1 gene codon G71R allele is a risk factor for Neonatal hyperbilirubinemia in the Chinese population.
- Cord blood bilirubin level in relation to bilirubin UDP-glucuronosyltransferase gene missense allele in Chinese neonates. Acta paediatrica (Oslo, Norway : 1992), 2007 Nov [Go to PubMed]
- To investigate bilirubin UDP-glucuronosyltransferase (UGT1A1) gene allele in healthy Chinese neonates, their cord bilirubin level and the subsequent hyperbilirubinemia to determine relationships among them.
Cord blood of 48 neonates was obtained to determine the exon 1 of UGT1A1 gene, total serum bilirubin, albumin, glutamic-pyruvic transaminase (GPT), glutamic-oxalacetic transaminase (GOT) and haemoglobin (Hb) concentration. Neonatal jaundice was assessed by measurement of transcutaneous bilirubin (TCB) and serum bilirubin. Neonates were divided into two groups according to mutant or normal allee to compare the variables.
Nineteen infants had the nucleotide 211 G-->A allele, 3 had the heterozygous variation (686C-->A, 845 A-->T, 231G-->A). In the 211 A allele group, cord bilirubin was significantly higher than in the 211 G allele group (p = 0.034), but there were no differences in albumin (p = 0.678), GPT (p = 0.460), GOT (p = 0.440) and Hb (p = 0.886). The TCB (at 48, 96 h), the frequency of the hyperbilirubinemia and prolonged jaundice were also significantly higher in the 211 A allele group.
The UGT1A1 gene codon G71R allele is a risk factor for neonatal hyperbilirubinemia in the Chinese population. Its effect on bilirubin metabolism may present early on, as well as late in foetal life. - 15491385
- UGT1A1
- mutation
- Diagnosis; Pathogenesis
- Method
- UGT1A1 gene, glycine to arginine at codon 1 (G71R
- Summary
- G71R mutation may not contribute to the high incidence of the Neonatal jaundice in South-east Asian populations
- Screening for G71R mutation of the UGT1A1 gene in the Javanese-Indonesian and Malay-Malaysian populations. Pediatrics international : official journal of the, 2004 Oct [Go to PubMed]
- There are significant differences in the prevalence and severity of neonatal jaundice among various populations. Recently, it has been reported that a mutation of the UGT1A1 gene, glycine to arginine at codon 1 (G71R), is related to the development of neonatal jaundice in East Asian populations. However, whether the G71R mutation contributes to the high incidence of neonatal jaundice in different Asian populations remains unknown. The authors screened for this mutation in the Javanese-Indonesian and Malay-Malaysian populations.
One hundred and thirty-six subjects were enrolled in this study: 68 Javanese-Indonesian adults and 68 Malay-Malaysian newborns (32 with jaundice and 36 without jaundice). Denaturing high-performance liquid chromatography (DHPLC) was used to screen for the G71R mutation, and the results were confirmed by nucleotide sequencing analysis.
With DHPLC, the authors easily and clearly detected seven subjects carrying the G71R mutation: two Javanese-Indonesian adults and five Malay-Malaysian newborns. In the 68 Javanese-Indonesian adults, the genotype distribution for G71R mutation was 66 G/G, two G/R and no R/R genotypes, and the mutated allele frequency was 0.015. In the 68 Malay-Malaysian newborns, genotype distribution for the mutation was 63 G/G, five G/R and no R/R genotypes, and the mutated allele frequency was 0.037. The genotype distributions did not differ significantly between the newborns with jaundice and those without jaundice.
The G71R mutation is present, but very rare, in Javanese-Indonesians and Malay-Malaysians. Thus, G71R mutation may not contribute to the high incidence of the neonatal jaundice in South-east Asian populations. DHPLC analysis is a very useful method for detecting the G71R mutation. - 16210851
- UGT1A1
- mutation
- Diagnosis; Pathogenesis
- Method
- A(TA)7TAA ,G71R ,G493R
- Summary
- Gilbert syndrome is caused by defects in the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene. These mutations differ among different populations and many of them have been found to be genetic risk factors for the development of Neonatal jaundice.
- Frequencies of A(TA)7TAA, G71R, and G493R mutations of the UGT1A1 gene in the Malaysian population. Biology of the neonate, 2006 [Go to PubMed]
- Gilbert syndrome is caused by defects in the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene. These mutations differ among different populations and many of them have been found to be genetic risk factors for the development of neonatal jaundice.
The objective was to determine the frequencies of the following mutations in the UGT1A1 gene: A(TA)7TAA (the most common cause of Gilbert syndrome in Caucasians), G71R (more common in the Japanese and Taiwanese population), and G493R (described in a homozygous Malay woman with Crigler-Najjar syndrome type 2) in a group of Malaysian babies with hyperbilirubinemia and a group of normal controls.
The GeneScan fragment analysis was used to detect the A(TA)7TAA variant. Mutation screening of both G71R and G493R was performed using denaturing high performance liquid chromatography.
Fourteen out of fifty-five neonates with hyperbilirubinemia (25%) carried the A(TA)7TAA mutation (10 heterozygous, 4 homozygous). Seven out of fifty controls (14%) carried this mutation (6 heterozygous, 1 homozygous). The allelic frequencies for hyperbilirubinemia and control patients were 16 and 8%, respectively (p=0.20). Heterozygosity for the G71R mutation was almost equal among both groups (5.5% for hyperbilirubinemia patients and 6.0% for controls; p=0.61). One subject (1.8%) in the hyperbilirubinemia group and none of the controls were heterozygous for the G493R mutation (p=0.476).
The A(TA)7TAA seems more common than the G71R and G493R mutations in the Malaysian population. - 20975617
- UGT1A1
- mutation
- Diagnosis; Pathogenesis
- Method
- NA
- Summary
- This suggests that neonates who carry the nucleotide 211 GA or AA variation within coding region in UGT1A1 gene are more susceptible to develop early-onset neonatal breastfeeding jaundice.
- 211 G to a variation of UDP-glucuronosyl transferase 1A1 gene and neonatal breastfeeding jaundice. Pediatric research, 2011 Feb [Go to PubMed]
- Breastfeeding jaundice is a common problem in neonates who were exclusively breastfed, but its pathogenesis is still unclear. The uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) gene polymorphism was shown to contribute to the development of neonatal hyperbilirubinemia. We hypothesize that the variation of UGT1A1 gene may contribute to neonatal breastfeeding jaundice. We prospectively enrolled 688 near-term and term infants who were exclusively breastfed (BF group) or were supplemented by infant formula partially (SF group) before onset of hyperbilirubinemia. Genotyping of the promoter and exon1 of UGT1A1 was performed in all neonates. Neonates in BF group had a significantly higher maximal body weight loss ratio, peak bilirubin level, and a greater incidence of hyperbilirubinemia than those in SF group. Neonates with nucleotide 211 GA or AA variation in UGT1A1 genotypes had higher peak serum bilirubin levels and higher incidence of hyperbilirubinemia than WTs (GG). This phenomenon was only seen inBF group but not in SF group when subset analysis was performed. This suggests that neonates who carry the nucleotide 211 GA or AA variation within coding region in UGT1A1 gene are more susceptible to develop early-onset neonatal breastfeeding jaundice.
- 24749086
- UGT1A1
- mutation
- Diagnosis; Pathogenesis
- Method
- homozygous p.G71R and heterozygous p.G71R.
- Summary
- The combination of homozygous p.Y486D and homozygous or heterozygous p.G71R is identified. The p.Y486D and p.G71R can be screened for the mutation analysis of UGT1A1 in Korean CN-2 patients.
- Molecular Analysis of the UGT1A1 Gene in Korean Patients with Crigler-Najjar Syndrome Type II. nutrition, 2014 Mar [Go to PubMed]
- Crigler-Najjar syndrome type II (CN-2) is characterized by moderate non-hemolytic unconjugated hyperbilirubinemia as a result of severe deficiency of bilirubin uridine diphosphate-glucuronosyltransferase (UGT1A1). The study investigated the mutation spectrum of UGT1A1 gene in Korean children with CN-2.
Five Korean CN-2 patients from five unrelated families and 50 healthy controls were enrolled. All five exons and flanking introns of the UGT1A1 gene were amplified by polymerase chain reaction (PCR) and the PCR products were directly sequenced.
All children initially presented with neonatal jaundice and had persistent indirect hyperbilirubinemia. Homozygous p.Y486D was identified in all five patients. Three patients had an associated homozygous p.G71R and two a heterozygous p.G71R. The allele frequency of p.Y486D and p.G71R in healthy controls was 0 and 0.16, respectively. No significant difference in mean serum bilirubin levels was found between homozygous carriers of p.G71R and heterozygous carriers.
The combination of homozygous p.Y486D and homozygous or heterozygous p.G71R is identified. The p.Y486D and p.G71R can be screened for the mutation analysis of UGT1A1 in Korean CN-2 patients. - 12139570
- UGT1A1
- mutation
- Diagnosis; Pathogenesis
- Method
- NA
- Summary
- ADD A NOTE
- Novel missense mutation of the UGT1A1 gene in Thai siblings with Gilbert's syndrome. Pediatrics international : official journal of the, 2002 Aug [Go to PubMed]
- Gilbert's syndrome is a common inherited disorder of bilirubin metabolism contributing to the development of neonatal jaundice and causing recurrent jaundice after the neonatal period. In the patients with Gilbert's syndrome, mutations have been reported in the promoter and exons of the uridine diphosphate-glucuronosyl transferase 1 (UGT1A1) gene on chromsome 2q37, which encodes bilirubin uridine diphosphate-glucuronosyltransferase. However, the genetic basis of Gilbert's syndrome, including its inheritance trait, remains to be clarified.
Patients 1 and 2 were Thai sisters with Gilbert's syndrome. They had a history of prolonged neonatal jaundice and showed recurrent jaundice after their infancy, while the parents showed no symptoms. To search for the mutation in the patients, all exons of the UGT1A1 gene were amplified by polymerase chain reaction (PCR) and sequenced directly. The frequency of the mutation in controls was studied by PCR-restriction enzyme digestion method.
The patients were homozygous for a novel single transition of T to C at nucleotide position 247 (exon 1), which would predict a substitution of leucine for phenylalanine at codon 83 of the enzyme protein. No other mutation was detected in any regions except exon 1. The parents with no symptoms showed heterozygosity for the mutation. Among the 110 Japanese controls, no homozygous individuals and three heterozygous individuals for the mutation were identified, giving a mutated allele frequency of 0.0136.
A novel missense mutation in the UGT1A1 gene was identified in two Thai siblings with Gilbert's syndrome. The affected family showed that homozygosity for the mutation may lead to apparent symptoms and that the syndrome was inherited as an autosomal recessive trait. The mutation does not explain a high incidence of neonatal jaundice in Japan, because it is very rare in the Japanese population. - 11061796
- UGT1A1
- mutation
- Diagnosis
- Method
- 211G-->A (G71R),1456T-->G (Y486D) ,and an enhancer
- Summary
- Sixteen the bilirubin UGT1A1 of infants with prolonged unconjugated hyperbilirubinemia,Seven were homozygous for 211G-->A (G71R), One was heterozygous for 1456T-->G (Y486D) and homozygous for 211G-->A. Six were heterozygous for 211G-->A. One was heterozygous for both 211G-->A and a TATA box mutation (A(TA)7TAA). One had a heterozygous mutation in an enhancer region (C-->A at -1353).
- Prolonged unconjugated hyperbilirubinemia associated with breast milk and mutations of the bilirubin uridine diphosphate- glucuronosyltransferase gene. Pediatrics, 2000 Nov [Go to PubMed]
- Breast milk jaundice is a common problem in nursing infants. It has been ascribed to various breast milk substances, but the component or combination of components that is responsible remains unknown. During our study of defects of the bilirubin uridine diphosphate-glucuronosyltransferase gene (UGT1A1) in patients with hereditary unconjugated hyperbilirubinemia (Crigler-Najjar syndrome and Gilbert's syndrome) and neonatal hyperbilirubinemia, we encountered a prolonged case associated with breastfeeding; after cessation of breastfeeding, the infant's bilirubin level became normal. Genetic analysis revealed a missense mutation identical to that found in patients with Gilbert's syndrome, which usually causes jaundice after puberty. We analyzed the bilirubin UGT1A1 of infants with prolonged unconjugated hyperbilirubinemia associated with breast milk to ascertain whether genetic factors are involved.
We analyzed 17 breastfed Japanese infants with apparent prolonged jaundice (total serum bilirubin concentrations above 171 micromol/L [10 mg/dL]) 3 weeks to 1 month after their birth. Except for jaundice, the infants were healthy and did not show evidence of hemolytic anemia, liver dysfunction, or hypothyroidism. After cessation of breastfeeding, the serum bilirubin concentration began to decrease in all cases. When breastfeeding was resumed, serum bilirubin concentration again became elevated in some infants, but the concentration fell to within normal by 4 months of age. We analyzed the polymerase chain reaction-amplified exon, promoter, and enhancer regions of UGT1A1 by direct sequencing.
Sixteen infants had at least one mutation of the UGT1A1. Seven were homozygous for 211G-->A (G71R), which is the most common mutation detected in the East Asian population, and the mutant enzyme had one third of the normal activity. G71R is the most common missense mutation we found in our analyses in Japanese patients with Gilbert's syndrome, and it corresponds to a UGT1A1 polymorphism in the Japanese population (the allele frequency is.16). One was heterozygous for 1456T-->G (Y486D) and homozygous for 211G-->A. Six were heterozygous for 211G-->A. One was heterozygous for both 211G-->A and a TATA box mutation (A(TA)7TAA). One had a heterozygous mutation in an enhancer region (C-->A at -1353). We did not detect a homozygous A(TA)7TAA mutation, which was the most common cause of Gilbert's syndrome in European population, in this study of Japanese infants with prolonged hyperbilirubinemia triggered by breast milk.
The results indicate that defects of UGT1A1 are an underlying cause of the prolonged unconjugated hyperbilirubinemia associated with breast milk. One or more components in the milk may trigger the jaundice in infants who have such mutations. The mutations we found were identical to those detected in patients with Gilbert's syndrome, a risk factor of neonatal nonphysiologic hyperbilirubinemia and a genetic factor in fasting hyperbilirubinemia. - 19325249
- UGT1A1
- mutation
- Diagnosis; Pathogenesis
- Method
- NA
- Summary
- There was a trend between the number of G71R mutations and the need for phototherapy.
- UGT1A1 haplotype mutation among Asians in Singapore. Neonatology, 2009 [Go to PubMed]
- The uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) enzyme is responsible for conjugation of the bilirubin in the liver as well as for drug metabolism. Some of the polymorphisms have been associated with an increased risk of neonatal hyperbilirubinemia which may explain the increased incidence of jaundice in an Asian population as well as exaggerated irinotecan-induced leukopenia.
The local Asian incidence of hypomorphic haplotypes, defined as gene mutations known to have a reduced function, has not been described. Clinical correlation between the mutations and the need for phototherapy for hyperbilirubinemia was carried out.
A cohort of 241 consecutive term infants delivered in the National University Hospital, Singapore, was recruited with parental consent. Cord blood was collected, and the promoter and coding regions of the UGT1A1 gene were sequenced.
Six known haplotypes and 2 novel haplotypes were identified: 1 wild type, 5 with reduced function, while the 2 novel ones were predicted to have decreased function. The frequency of these hypomorphic haplotypes was high. Among the 241 infants screened, 35% had 1 hypomorphic haplotype and 12% had 2 hypomorphic haplotypes. The frequency was also different among ethnic groups, with 48% Chinese, 64% Indian and 31% Malay infants having at least 1 hypomorphic haplotype (chi(2) test, p < 0.05). There was a trend seen between the number of G71R mutations and the need for phototherapy (chi2 test for trend, p < 0.05).
The local Asian incidence of hypomorphic haplotypes was high and there was a trend between the number of G71R mutations and the need for phototherapy. The G71R mutation may account for the increased incidence of neonatal jaundice seen in Asian populations. - 22407023
- UGT1A1
- mutation
- Diagnosis
- Method
- NA
- Summary
- We emphasize that investigating both the UGT1A gene and G6PD activity is the most reliable way to make a correct differential Diagnosis.
- Study of a family in the province of Matera presenting with glucose-6-phosphate dehydrogenase deficiency and Gilbert's syndrome. Molecular medicine reports, 2012 Jun [Go to PubMed]
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency, a recessive X-linked trait, is the most common enzyme deficiency in the world. The most devastating clinical consequence of this deficit is severe neonatal jaundice, which results in sensorineural deficit, and severe haemolytic anemia. However, patients may be asymptomatic. The most common clinical sign is hyperbilirubinemia (h↑), that is also related to Gilbert's syndrome, a condition associated with the promoter polymorphism of the UDP-glucuronosyltransferase 1 (UGT1A1) gene. The aim of this study was to underline (as is usually done by DNA molecular analysis) to detect and to clarify the genetic deficiency that is the reason of the disorder in question. In this study, different techniques were applied to analyse a family of four individuals presenting with hyperbilirubinemia: bilirubinic dosage, electrophoresis and enzymatic activity dosage of G6PD; molecular analysis of the UGT1A promoter to detect a thymine-adenine (TA) insertion, that causes the[A(TA)7TAA] mutation. The results showed that in certain cases, the presence of hyperbilirubinemia is not only associated with G6PD deficiency, but may be caused by the co-presence of a mutation in the UGTA1 promoter related to Gilbert's syndrome. As being affected by these two conditions predisposes to adverse effects towards certain drug treatments, it is advisable to study the UGTA1 gene before prescribing drugs for specific antineoplastic or retroviral treatment. We emphasize that investigating both the UGT1A gene and G6PD activity is the most reliable way to make a correct differential diagnosis.
- 11174102
- UGT1A1
- mutation
- Diagnosis
- Method
- NA
- Summary
- Gilbert syndrome (GS), characterized by mild, chronic and isolated unconjugated hyperbilirubinemia is due to a partial deficiency of bilirubin-UDP-glucuronosyltransferase (UGT1A1).
- [Refinement and role of the diagnosis of Gilbert disease with molecular biology]. Annales de biologie clinique, [Go to PubMed]
- Gilbert syndrome (GS), characterized by mild, chronic and isolated unconjugated hyperbilirubinemia is due to a partial deficiency of bilirubin-UDP-glucuronosyltransferase (UGT1A1). Recently, the genetic basis of GS has been identified in caucasian populations : it is related to the insertion of a dinucleotide (TA) in the promoter region of the UGT1A1 gene. In Asian populations, GS is due to missense mutations (either homozygous or heterozygous) in the coding sequence. The aim of this study was to develop a simple and rapid method to detect both genetic polymorphisms and mutations. This technique was performed (1) to explore unrelated unconjugated hyperbilirubinemia; (2) to evaluate the frequency of GS in a population of 97 healthy caucasian volunteers: 17% of them were homozygous for the TA7/TA7 polymorphism; (3) to determine the incidence of this syndrome in a population of 105 neonates with unconjugated hyperbilirubinemia. The incidence of GS (15%) was not significantly higher than it was in the control grup. A correlation between GS genotype and neonatal jaundice was not established; (4) to seek a relationship between GS and preeclampsia with or without Hellp syndrome. The incidence in the Hellp syndrome group (n = 19) was 26%, two fold higher than in preeclampsia group (n = 22) and control group (n = 50) with only 14% and 13% respectively, (5) to start a study regarding the toxicity of irinotecan treatment in a population of homozygous children for the UGT1A1 polymorphism.
- 16623861
- UGT1A1
- mutation
- Diagnosis; Pathogenesis
- Method
- NA
- Summary
- Our results do not suggest an association between thymine-adenine repeat Polymorphism of UGT1A1 and hyperbilirubinaemia of unexplained aetiology or prolonged jaundice in Turkish neonates.
- Neonatal jaundice and bilirubin UDP-glucuronosyl transferase 1A1 gene polymorphism in Turkish patients. toxicology, 2006 Apr [Go to PubMed]
- Bilirubin uridine diphosphate-glucuronosyltransferase (B-UGT) is the rate-limiting enzyme for the conjugation of bilirubin with glucuronic acid in its excretion process into the bile. Variations in B-UGT gene (UGT-1A1) have been related to disorders characterised by hyperbilirubinaemia. The aim of this study was to investigate whether the number of thymine-adenine repeats in the promoter region of UGT-1A1 was related to non-physiologic hyperbilirubinemia of unexplained aetiology in Turkish newborns. These patients (n=106) were genotyped for their thymine-adenine repeat number in the promoter region of UGT-1A1, and were divided into two groups according to their bilirubin level. Forty-nine newborns with bilirubin levels higher than 17 mg/dl within the first ten days of life comprised the hyperbilirubinaemia group and 25 newborns with bilirubin levels higher than 10 mg/dl after fifteen days of life formed the prolonged jaundice group. Thirty-two newborns were included as healthy controls. The observed frequences for the wild-type six repeat allele thymine-adenine (TA(6)) within each subject group were similar (P>0.05; 75.5%, 78.0% and 73.4%, respectively). Likewise, the distribution of TA(6/6), TA(6/7) and TA(7/7) genotypes among three groups were similar. These results imply that the TA(7) repeat allele of UGT1A1 (UGT1A1*28) is a common variant in the Turkish population. Our results do not suggest an association between thymine-adenine repeat polymorphism of UGT1A1 and hyperbilirubinaemia of unexplained aetiology or prolonged jaundice in Turkish neonates.
- 12357057
- UGT1A1
- mutation
- Diagnosis; Pathogenesis
- Method
- variation in the promoter, variation at nucleotide
- Summary
- In conclusion, this study has demonstrated that variation at nucleotide 211 of the UGT1A1 gene is a risk factor for the development of Neonatal hyperbilirubinemia.
- Relationship between bilirubin UDP-glucuronosyl transferase 1A1 gene and neonatal hyperbilirubinemia. Pediatric research, 2002 Oct [Go to PubMed]
- The variation rate within the coding region of UDP-glucuronosyl transferase 1A1 (UGT1A1) gene in Taiwan Chinese was found to be 29.3%. This study sought to determine whether that high variation rate of UGT1A1 gene is a risk factor for neonatal hyperbilirubinemia. The study subjects consisted of 123 newborn infants suffering from unconjugated hyperbilirubinemia who had no known risk factors for hyperbilirubinemia and 218 healthy control neonates. The promoter area, exons 1 to 4, coding region of exon 5, and the flanking intronic regions in UGT1A1 gene were determined by the PCR in all subjects. Wild UGT1A1 gene, variation in the promoter, variation at nucleotide 211, variation at nucleotide 1091, and compound heterozygous variation of UGT1A1 gene were found. The percentage of neonates with wild UGT1A1 gene and the percentage of neonates with variation at nucleotide 211 were significantly different between the study subjects and controls. The percentages with bilirubin >or=342 micro M (20.0 mg/dL) and with persistent hyperbilirubinemia in the subjects carrying homozygous variation at nucleotide 211 (Gly71Arg) were significantly higher than the neonates carrying wild type or other genotypes. In conclusion, this study has demonstrated that variation at nucleotide 211 of the UGT1A1 gene is a risk factor for the development of neonatal hyperbilirubinemia. Pediatricians should closely follow hyperbilirubinemic newborn infants who carry homozygous 211 G to A variation in UGT1A1 gene.
- 10190918
- UGT1A1
- mutation
- Diagnosis; Pathogenesis
- Method
- UGT1A1 TATA alleles (TA6 and TA7) and a novel TAT
- Summary
- A genetic predisposition to develop prolonged Neonatal hyperbilirubinemia in breast-fed infants is associated with TATA box Polymorphism of the UGT1A1 gene and will be recognized as Gilbert's syndrome in adulthood and In addition to the known common UGT1A1 TATA alleles (TA6 and TA7), a novel TATA allele (TA5) in a neonate with very prolonged jaundice was identified.
- Gilbert's syndrome is a contributory factor in prolonged unconjugated hyperbilirubinemia of the newborn. The Journal of pediatrics, 1999 Apr [Go to PubMed]
- Prolonged neonatal jaundice, beyond day 14 of life, is very common and of concern to the clinician. The aim of this study was to investigate whether a genetic mutation in the bilirubin UGT1A1 gene, which has been associated with Gilbert's syndrome in adults, is a contributory factor in prolonged neonatal jaundice.
Blood was collected from 85 term newborns with unexplained hyperbilirubinemia, and DNA was prepared. The neonates were divided into 6 groups depending on whether they were breast-fed or bottle-fed and whether they had acute, prolonged, or very prolonged jaundice. UGT1A1 TATA promoter genotyping (DNA test for Gilbert's syndrome) was performed on all samples, and analysis of the entire UGT1A1 coding sequence was performed in a representative sample (11 of 26) of very prolonged cases.
In addition to the known common UGT1A1 TATA alleles (TA6 and TA7), a novel TATA allele (TA5) in a neonate with very prolonged jaundice was identified. Statistical analysis of the TATA genotype distributions within the group of breast-fed neonates revealed significant differences among the acute, prolonged, and very prolonged subgroups (.05 > P >.01): the incidence of familial hyperbilirubinemia genotypes (7/7 and 5/7) is 5 times greater in very prolonged cases (31%) relative to acute cases (6%). Neonates with prolonged jaundice from family pedigrees were observed to demonstrate the Gilbert's phenotype as children or young adults.
A genetic predisposition to develop prolonged neonatal hyperbilirubinemia in breast-fed infants is associated with TATA box polymorphism of the UGT1A1 gene and will be recognized as Gilbert's syndrome in adulthood. - 24783083
- UGT1A1
- mutation
- Diagnosis; inactive stage; Pathogenesis
- Method
- The promoter and coding regions of Uridine diphosp
- Summary
- We showed that in Gloucose-6-Phosphate Dehydrogenase (G6PD) deficient neonates, there was no significant association between Gilbert's syndrome (promoter Polymorphism) and hyperbilirubinemia.
- Relation between Neonatal Icter and Gilbert Syndrome in Gloucose-6-Phosphate Dehydrogenase Deficient Subjects. Journal of clinical and diagnostic research : JCDR, 2014 Mar [Go to PubMed]
- The pathogenesis of neonatal hyperbilirubinemia hasn't been completely defined in Gloucose-6-Phosphate Dehydrogenase (G6PD) deficient newborns. The aim of this study was to detect the relationship between Gilbert's syndrome and hyperbilirubinemia in Gloucose-6-Phosphate Dehydrogenase (G6PD) deficient neonates.
This case-control study was conducted in Amirkola pediatrics teaching hospital, Babol, Iran. A total number of one hundred four infants were included in the study (51 infants with neonatal jaundice and Gloucose-6-Phosphate Dehydrogenase (G6PD) deficiency admitted to phototherapy or transfusion were selected as the case group and 53 infants with Gloucose-6-Phosphate Dehydrogenase (G6PD) deficiency admitted for other reasons than jaundice were selected as the control group). Exclusion criteria were ABO or Rh incompatibility or other reasons that made Coombs test positive, sepsis, hepatosplenomegaly, metabolic diseases, medical treatment and phototherapy. The promoter and coding regions of Uridine diphosphate Glucuronosyl Transferase 1A1 (UGT1A1) of genomic DNA were amplified by polymerase chain reaction (PCR) isolated from leukocytes. We used chi-square test and t-test to compare cases and controls.
Distribution of Gilbert genome was not significantly different between the two groups; among cases, 33.3% were homozygote, 35.3% heterozygote, and 31.4% normal. Among controls, 22.6% were homozygote, 34% heterozygote, and 43.4% normal (p-value=xxx). Hyperbilirubinemia family history didn't differ significantly between these two groups.
We showed that in Gloucose-6-Phosphate Dehydrogenase (G6PD) deficient neonates, there was no significant association between Gilbert's syndrome (promoter polymorphism) and hyperbilirubinemia. - 20061399
- UGT1A1
- mutation
- Diagnosis; inactive stage; Pathogenesis
- Method
- promoter region of UGT1A1 gene
- Summary
- In this sample, the variants of UGT1A1 were not associated to severe hyperbilirubinemia;
- Polymorphic variants of UGT1A1 in neonatal jaundice in southern Brazil. Journal of tropical pediatrics, 2010 Oct [Go to PubMed]
- Alterations in the hepatic conjugation of bilirubin due to uridyl-diphosphate-glucuronosyltransferase 1A1 (UGT1A1) polymorphisms have been proposed as risk factors to neonatal jaundice. Herein, we estimated the frequency of genotypes of the promoter region of UGT1A1 gene in newborns and evaluated its association with severe hyperbilirubinemia. Prospective study of cases and controls including all newborns admitted for phototherapy at HCPA, Brazil, during 9 months; 490 babies were enrolled and PCR was performed. Polymorphic genotypes were detected in 16% of the patients and 7 of the 10 possible genotypes were identified with higher prevalence of polymorphisms in Afro-descendants. In this sample, the variants of UGT1A1 were not associated to severe hyperbilirubinemia; other genic factors should be sought in this high miscegenation area of Brazil.
- 12743455
- UGT1A1
- mutation
- Diagnosis; Pathogenesis
- Method
- NA
- Summary
- In conclusion, we showed that TA 7/7 and TA 6/7 genotypes are not rare in our population and that the presence of thes Polymorphisms alone does not play a significant role in the etiology of unexplained pathologic or prolonged Neonatal hyperbilirubinemia.
- Analyses of polymorphism for UGT1*1 exon 1 promoter in neonates with pathologic and prolonged jaundice. Biology of the neonate, 2003 [Go to PubMed]
- In this study, we investigated whether a TATA box polymorphism in the promoter of the UGT1*1 exon I, the most common detected DNA polymorphism in Gilbert's syndrome, is a contributory factor in unexplained pathologic or prolonged jaundice. 38 neonates who had unexplained pathologic jaundice, 37 neonates who had unexplained prolonged jaundice, and 35 healthy, nonjaundiced neonates were enrolled in the study. Genotypes were assigned as follows: 6/6 (homozygous for a normal allele bearing the sequence [TA](6)TAA), 7/7 (homozygous for an abnormal allele with the sequence [TA](7)TAA), and 6/7 (heterozygous with one of each allele). Of the 110 infants, 10 (9%) had 7/7, 51 (46%) had 6/7, and 49 (45%) had 6/6 genotype; the differences between the three groups were not statistically significant. Also no differences were observed among different genotypes and mean serum total bilirubin concentrations. In conclusion, we showed that TA 7/7 and TA 6/7 genotypes are not rare in our population and that the presence of thes polymorphisms alone does not play a significant role in the etiology of unexplained pathologic or prolonged neonatal hyperbilirubinemia.
- 15319464
- UGT1A1
- mutation
- Diagnosis; Pathogenesis
- Method
- NA
- Summary
- The incidence of severe Neonatal hyperbilirubinemia is higher in Asians than in whites.
- Risk factors for severe hyperbilirubinemia in neonates. Pediatric research, 2004 Nov [Go to PubMed]
- The incidence of severe neonatal hyperbilirubinemia is higher in Asians than in whites. A case-control study was designed to investigate the effects of eight known risk factors [breast feeding, ABO incompatibility, premature birth, infection, cephalohematoma, asphyxia, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and variant UDP-glucuronosyltransferase 1A1 (UGT1A1) gene] and a suspicious analog [organic anion transporter 2 (OATP 2) gene] on severe hyperbilirubinemia in Taiwanese neonates. The 72 study subjects and 100 hospital control subjects consisted of neonates with peak serum bilirubin levels > or =342 microM and <256.5 microM, respectively. The PCR-restriction fragment length polymorphism method was applied to detect the UGT1A1, OATP 2, and G6PD genes. The results of multivariate logistic regressions, adjusted for covariates, revealed odds ratios (ORs) of 4.64 [95% confidence interval (CI): 2.25-9.57; p < 0.001], 3.36 (95% CI: 1.54-7.35; p=0.002), and 3.02 (95% CI: 1.30-6.99; p=0.010) for neonates who were fed with breast milk, and carry the variant UGT1A1 gene at nucleotide 211 and the variant OATP 2 gene at nucleotide 388, respectively. The ORs, adjusted for covariates, for the other six risk factors were not statistically significant. The ORs in neonates who had one, two, and three significant risk factors were 8.46 (95% CI: 2.75-34.48; p < 0.001), 22.0 (95% CI: 5.50-88.0; p < 0.001), and 88.0 (95% CI: 12.50-642.50; p < 0.001), respectively. In conclusion, neonates who carry the 211 and 388 variants in the UGT1A1 and OATP 2 genes, respectively, as well as feed with breast milk are at high risk to develop severe hyperbilirubinemia.
23 pubmed articles have reported UGT1A1 mutation associated with Neonatal Jaundice.