Screening for G71R mutation of the UGT1A1 gene in the Javanese‐Indonesian and Malay‐Malaysian populations

Sutomo, Retno; Talib, Norlelawati A.; Yusoff, Narazah Mohd; Rostenberghe, Hans Van; Sadewa, Ahmad Hamim; Sunarti, Sunarti; Sofro, Abdul Salam M.; Yokoyama, Naoki; Lee, Myeong J.; Matsuo, Masafumi; Nishio, Hisahide

doi:10.1111/j.1442-200x.2004.01959.x

Cited by 20 publications

(21 citation statements)

References 24 publications

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“…11 The 211G4A (G71R) was found at a frequency of 14.8% over the combined groups, which is consistent with the frequency of 13-23% found in other Asian populations. 10,12,13 The variant 686C4A was very rare in all the ethnic groups, with a frequency varying from 0.9 to 2.2%, similar to previous data. 10,11 Strong LD was found between the five polymorphisms but with lower r 2 values except for between À3156G4A and (TA)647 (r 2 ¼ 0.88) which is consistent with a recent study.…”

Section: Intra-ethnic Differences In Genetic Variantssupporting

confidence: 89%

Intra-ethnic differences in genetic variants of the UGT-glucuronosyltransferase 1A1 gene in Chinese populations

et al. 2006

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Variants within the human UGT1A1 gene are associated with irinotecan induced severely adverse reactions and hyperbilirubinemia. Intra-ethnic differences in the genetic variation and haplotypes of UGT1A1 gene have been analyzed in the present study. Relationship between the concentrations of total serum bilirubin (T-bil) and haplotype structure of UGT1A1 in healthy people were also evaluated. We genotyped five functional polymorphisms including À3279T4G and À3156G4A in the enhancer region, (TA)647 in the TATA box, and 211G4A (G71R), 686C4A (P229Q) in the exon1 region of UGT1A1 in three groups of healthy Chinese ethnic populations, consisting of 264 subjects of She origin, 539 of Han origin and 273 of Dong origin. The distribution of À3279T4G, (TA)647, 211G4A of UGT1A1 differed greatly as between the three ethnic groups. All of six haplotypes differed considerably between at least two of the three groups, which highlighted the need to analyze clinically irinotecan toxicity relevant SNPs and haplotypes in a variety of different racial groups within the Chinese population. Total bilirubin concentration in homozygous carriers of the À3279G and (TA)7 allele were significantly higher than those in heterozygous carriers or homozygous carriers of wild-type alleles. Carriers of the variant haplotypes (À3279G; À3156A; (TA)7; 211G; 686C) had higher serum T-Bil concentrations compared with the other groups. Our results indicate that heterogeneity among different ethnic populations is possibly the result of microevolution and is relevant to studies into the effect of tailored drug treatment.

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Section: Intra-ethnic Differences In Genetic Variantssupporting

confidence: 89%

Intra-ethnic differences in genetic variants of the UGT-glucuronosyltransferase 1A1 gene in Chinese populations

et al. 2006

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“…But some other studies reported no relationship between Gilbert syndrome and G6PD deficiency [5,9,14,15]; their findings were similar to the present study and no significant differences were observed between icteric and non-icteric neonates with regards to the Gilbert homozygoticity or hetrozygoticity.…”

Section: Methodssupporting

confidence: 80%

Relation between Neonatal Icter and Gilbert Syndrome in Gloucose-6-Phosphate Dehydrogenase Deficient Subjects

Zahedpasha

Ahmadpour

Akhavan‐Niaki

et al. 2014

JCDR

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Background and Aim: The pathogenesis of neonatal hyper bilirubinemia 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. Materials and Methods:This case control study was con ducted 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.Results: 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.

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“…With regard to mutations in the coding region of UGT1A1, we previously reported that the c.211GϾA mutation is rare in Malays and Javanese (13,14). However, according to recent reports in the Chinese population in Malaysia and Singapore, the c.211GϾA mutation is observed more frequent than Malays and Javanese (26 -28).…”

Section: Discussionmentioning

confidence: 85%

“…Although several studies of the A(TA)7TAA and c.211GϾA mutations in the Southeast Asian population have been reported (13,14), the c.-3279TϾG and c.-3156GϾA mutations have never been examined in this population. Therefore, we determined the genotypes of the mutations, c.-3279TϾG, c.-3156GϾA, and A(TA)7TAA, in Malay infants with or without neonatal jaundice to evaluate the contribution of the mutations of the UGT1A1 promoter to the development of neonatal jaundice.…”

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confidence: 99%

A Polymorphic Mutation, c.-3279T>G, in the UGT1A1 Promoter Is a Risk Factor for Neonatal Jaundice in the Malay Population

et al. 2010

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ABSTRACT: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.-3279TϾG, c.-3156GϾA, and A(TA)7TAA in Malay infants with neonatal jaundice (patients) and in infants without neonatal jaundice (controls). In our population study, only c.-3279TϾG was associated with neonatal jaundice. The genotype distributions between both groups were significantly different (p ϭ 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 ϭ 0.006). We then investigated changes in transcriptional activity because of c.-3279TϾG. 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.-3279TϾG modified the synergistic effects of the nuclear factors associated with transcriptional machinery. In conclusion, the c.-3279TϾG mutation in the UGT1A1 promoter is a genetic risk factor for neonatal jaundice. T he uridine diphospho (UDP)-glucuronate-glucuronosyltransferase 1A1 (UGT1A1) gene encodes bilirubin UDPglucuronosyltransferase (UGT1A1), which is the enzyme responsible for bilirubin glucuronidation. A decrease in UGT1A1 activity leads to unconjugated hyperbilirubinemia. Inherited UGT1A1 deficiencies because of UGT1A1 mutations are classified into three forms based on clinical severity: Crigler-Najjar syndrome type 1 (CN-1, a severe form), Crigler-Najjar syndrome type 2 (CN-2, an intermediate form), and Gilbert's syndrome (GS, a mild form) (1,2). Such inherited UGT1A1 deficiencies may cause neonatal jaundice.A mutant TATA box with an additional TA insertion, A(TA)7TAA, was first found in patients with CN-1, CN-2, and GS (3-5). GS with homozygosity for A(TA)7TAA accelerates or prolongs neonatal jaundice (6). This mutation is frequently observed in whites and Africans (7). Another GScausing gene mutation, c.211GϾA, is frequent in the East Asian population (8). The c.211GϾA mutation causes an amino acid change, glycine to arginine at codon 71.Recently, polymorphic mutations, c.-3279TϾG and c.-3156GϾA, were identified in the UGT1A1 promoter region (9,10). The c.-3279TϾG mutation is located in the phenobarbital responsive enhancer module (gtPBREM), which is activated by a nuclear receptor, constitutive androstane receptor (CAR) (11). Sugatani et al. (9) showed using luciferase reporter assay that mutant gtPBREM with c.-3279TϾG decreases the transcriptional activity of the UGT1A1 promoter by 60%. The c.-3156GϾA mutation is located between the gtPBREM and TATA box. A haplotype analysis showed that there is a high extent of linkage disequilibrium between c.-3156GϾA and A(TA)7TAA (10,12). However, it is unknown ...

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Screening for G71R mutation of the UGT1A1 gene in the Javanese‐Indonesian and Malay‐Malaysian populations

Abstract: 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.

Cited by 20 publications

References 24 publications

Intra-ethnic differences in genetic variants of the UGT-glucuronosyltransferase 1A1 gene in Chinese populations

Intra-ethnic differences in genetic variants of the UGT-glucuronosyltransferase 1A1 gene in Chinese populations

Relation between Neonatal Icter and Gilbert Syndrome in Gloucose-6-Phosphate Dehydrogenase Deficient Subjects

A Polymorphic Mutation, c.-3279T>G, in the UGT1A1 Promoter Is a Risk Factor for Neonatal Jaundice in the Malay Population

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