Neonatal hyperbilirubinemia and mutation of the bilirubin uridine diphosphate‐glucuronosyltransferase gene: a common missense mutation among Japanese, Koreans and Chinese

Akaba, Kazuhiro; Kimura, Toshiyuki; Sasaki, Ayako; Tanabe, Saori; Ikegami, Tohru; Hashimoto, Motoya; Umeda, Hitoshi; Yoshida, Hiroshi; Umetsu, Kazuo; Chiba, Hitoshi; Yuasa, Isao; Hayasaka, Kiyoshi

doi:10.1080/15216549800203512

Cited by 134 publications

(183 citation statements)

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“…(TA)7 insertion mutations are common in Caucasians and Africans but rare in East Asians (8,(21)(22)(23). Although (TA)7 insertion mutation was the second common mutation in this study, (TA)7/7 homozygous individuals were rare as well.…”

Section: Articlesmentioning

confidence: 71%

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UGT1A1 gene mutations and neonatal hyperbilirubinemia in Guangxi Heiyi Zhuang and Han populations

Zhong

Xie

et al. 2015

Pediatr Res

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Articles Population Study nature publishing groupBackground: Uridine diphosphoglucuronate-glucuronosyltransferase 1A1 (UGT1A1) gene mutation was shown to be responsible for neonatal hyperbilirubinemia. This study aimed to investigate whether UGT1A1 gene mutation is associated with neonatal hyperbilirubinemia in Guangxi Heiyi Zhuang and Han populations. Methods: Two hundred and eighteen infants with hyperbilirubinemia (118 Heiyi Zhuang, 100 Han) and 190 control subjects (110 Heiyi Zhuang, 80 Han) were enrolled. Polymerase chain reaction and gene sequencing were used to detect the TATA-box and exon 1 of UGT1A1. results: (TA)7 insertion mutation, 211G>A (G71R), 686C>A (P229Q), and 189C>T (D63D) were detected. Logistic regression analysis showed odds ratios (OR) of 2.64 (95% confidence interval (CI) 1.64-4.24; P < 0.001) and 0.69 (95%CI 0.43-1.10; P = 0.115) for neonates who carried UGT1A1 G71R and (TA)7 insertion mutation, respectively. G71R homozygosity increased the odds of dangerous bilirubin levels by a factor 34.23, and G71R heterozygosity only by 2.10. conclusion: We found that UGT1A1 G71R mutation is a risk factor for neonatal hyperbilirubinemia in Guangxi Heiyi Zhuang and Han populations. Meanwhile, the UGT1A1 (TA)7 insertion mutation is not associated with neonatal hyperbilirubinemia in the two ethnic groups.

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Section: Articlesmentioning

confidence: 71%

“…The (TA)7 insertion in the UGT1A1 promoter is the most common mutation in Caucasians, and appears to cause Gilbert's syndrome (6,7). Meanwhile, the G71R substitution in exon 1 of the UGT1A1 gene is the most common mutation type described as a risk factor for neonatal hyperbilirubinemia in Asians (8,9).…”

mentioning

confidence: 99%

UGT1A1 gene mutations and neonatal hyperbilirubinemia in Guangxi Heiyi Zhuang and Han populations

Zhong

Xie

et al. 2015

Pediatr Res

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“…The UGT1A1*6 variant is found almost exclusively in Asian populations, with a frequency of 0.13-0.25. 18 The UGT1A1*6 Table a. Variance explained was calculated as the proportion of the variance of log-transformed serum total bilirubin explained by the variable.…”

Section: Discussionmentioning

confidence: 99%

Association study between single-nucleotide polymorphisms in 199 drug-related genes and commonly measured quantitative traits of 752 healthy Japanese subjects

2009

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With dense single-nucleotide polymorphism (SNP) maps for 199 drug-related genes, we examined associations between 4190 SNPs and 38 commonly measured quantitative traits using data from 752 healthy Japanese subjects. On analysis, we observed a strong association between five SNPs within the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene and serum total bilirubin levels (minimum P-value in Mann-Whitney test¼1.82Â10 10 ). UGT1A1 catalyzes the conjugation of bilirubin with glucuronic acid, thus enhancing bilirubin elimination. This enzyme is known to play an important role in the variation of serum bilirubin levels. The five SNPs, including a nonsynonymous SNP-rs4148323 (211G4A or G71R variant allele known as UGT1A1*6)-showed strong linkage disequilibrium with each other. No other genes were clearly associated with serum total bilirubin levels. Results of linear multiple regression analysis on serum total bilirubin levels followed by analysis of variance showed that at least 13% of the variance in serum total bilirubin levels could be explained by three haplotype-tagging SNPs in the UGT1A1 gene.

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“…This mutation is predominant in Japanese and does not seem to be linked to the A(TA) 7 TAA polymorphic site. [119][120][121] Polymorphisms of the UGT1A1 Gene as Risk Factors for Drug-Induced Toxicity Patients affected by Gilbert's syndrome display lower glucuronidation rates for a number of therapeutic drugs including acetaminophen, tolbutamide and lorazepam. [20][21][22][34][35][36][37] Since Gilbert's syndrome is associated with the UGT1A1*28 (TA 7 polymorphism), it is more likely that patients with this allele will present an altered drug clearance compared to patients with the wild-type genotype.…”

Section: Ugt1a1mentioning

confidence: 99%

Pharmacogenomics of human UDP-glucuronosyltransferase enzymes

2003

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UDP-glucuronosyltransferase (UGT) enzymes comprise a superfamily of key proteins that catalyze the glucuronidation reaction on a wide range of structurally diverse endogenous and exogenous chemicals. Glucuronidation is one of the major phase II drug-metabolizing reactions that contributes to drug biotransformation. This biochemical process is also involved in the protection against environmental toxicants, carcinogens, dietary toxins and participates in the homeostasis of numerous endogenous molecules, including bilirubin, steroid hormones and biliary acids. Over the years, significant progress was made in the field of glucuronidation, especially with regard to the identification of human UGTs, study of their tissue distribution and substrate specificities. More recently, the degree of allelic diversity has also been revealed for several human UGT genes. Some polymorphic UGTs have demonstrated a significant pharmacological impact in addition to being relevant to drug-induced adverse reactions and cancer susceptibility. This review focuses on human UGTs, the description of the nature of polymorphic variations and their functional impact. The pharmacogenomic implication of polymorphic UGTs is presented, more specifically the role of UGT polymorphisms in modifying cancer risk and their impact on individual risk to drug-induced toxicities.

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Neonatal hyperbilirubinemia and mutation of the bilirubin uridine diphosphate‐glucuronosyltransferase gene: a common missense mutation among Japanese, Koreans and Chinese

Cited by 134 publications

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UGT1A1 gene mutations and neonatal hyperbilirubinemia in Guangxi Heiyi Zhuang and Han populations

UGT1A1 gene mutations and neonatal hyperbilirubinemia in Guangxi Heiyi Zhuang and Han populations

Association study between single-nucleotide polymorphisms in 199 drug-related genes and commonly measured quantitative traits of 752 healthy Japanese subjects

Pharmacogenomics of human UDP-glucuronosyltransferase enzymes

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