Dataset Information

Analysis of the UGT1A1 Genotype in Hyperbilirubinemia Patients: Differences in Allele Frequency and Distribution.

ABSTRACT: Objective:The spectrum of UDP-glucuronyl transferase A1 (UGT1A1) variants in hereditary unconjugated hyperbilirubinemia varies markedly between different ethnic populations. This study evaluated the UGT1A1 genotypes in hyperbilirubinemia patients from southeastern China. Methods:We enrolled 60 patients from southeastern China (44 men and 16 women; age range: 3-76 years) with unconjugated hyperbilirubinemia and performed genetic analysis of the UGT1A1 gene by direct sequencing. Results:For patients with Gilbert syndrome, 85% (47/55) harbored pathogenic variants of UGT1A1?60. Both UGT1A1?28 and UGT1A1?81 were detected in the promoter region of UGT1A1. Additionally, 83% (20/24) of patients with Gilbert syndrome heterozygous for UGT1A1?60 had an association with heterozygous variation of UGT1A1?28 or UGT1A1?81, while 91% (21/23) of Gilbert syndrome patients homozygous for UGT1A1?60 had biallelic variations of UGT1A1?28 and UGT1A1?81. We detected 213 UGT1A1 allelic variants, including six novel variations, with the most frequent allele being the UGT1A1?60, followed by UGT1A1?28 and UGT1A1?6. All of the patients showed multiple sites of variants in UGT1A1; however, variation number was not associated with bilirubin levels (P>0.05). Conclusions:The spectrum of UGT1A1 variants in southeastern Chinese patients was distinct from other ethnic populations. Our findings broaden the knowledge concerning traits associated with UGT1A1 variants and help profile genotype-phenotype correlations in hyperbilirubinemia patients.

SUBMITTER: Mi XX

PROVIDER: S-EPMC6699345 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Analysis of the <i>UGT1A1</i> Genotype in Hyperbilirubinemia Patients: Differences in Allele Frequency and Distribution.

Mi Xiao-Xiao XX Yan Jian J Ma Xiao-Jie XJ Zhu Ge-Li GL Gao Yi-Dan YD Yang Wen-Jun WJ Kong Xiao-Wen XW Chen Gong-Ying GY Shi Jun-Ping JP Shi Jun-Ping JP Gong Ling L

BioMed research international 20190729

<h4>Objective</h4>The spectrum of <i>UDP-glucuronyl transferase A1</i> (<i>UGT1A1</i>) variants in hereditary unconjugated hyperbilirubinemia varies markedly between different ethnic populations. This study evaluated the <i>UGT1A1</i> genotypes in hyperbilirubinemia patients from southeastern China.<h4>Methods</h4>We enrolled 60 patients from southeastern China (44 men and 16 women; age range: 3-76 years) with unconjugated hyperbilirubinemia and performed genetic analysis of the <i>UGT1A1</i> ge ...[more]

PMID: 31467903

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Project description:To retrospectively analyze and quantitatively correlate UGT1A1 (bilirubin UDP- glucuronosyltransferase gene) genotypes and unconjugated hyperbilirubinemia (UCH) phenotypes among Chinese children.We retrospectively reviewed UCH patients, quantitatively analyzed genotype-phenotype correlation by comparing with healthy controls. Pfam database, SWISS-model, and Pymol were used for UGT1A1 protein domain analysis and protein modeling for assessing the effect of novel missense variants on protein structure.Seventy four cases, including 21 prolonged unconjugated hyperbilirubinemia (PUCH), 30 Gilbert syndrome (GS), 22 Crigler-Najjar syndrome type II (CNS-II), and 1 Crigler-Najjar syndrome type I (CNS-I) phenotypes were analyzed. Total of 21 variants, including 7 novel variants (c.764T>A/p.L255Q, c.1112C>T/p.T371I, c.1028C>A/p.S343X, c.1047delG/p.I350YfsX16, c.996 + 5G>C/g.6923G>C, c.287G>A/p.G96E, and c.1142G>A/p.S381N) were found. In the multiple regression model, heterozygous A(TA)7TAA, G71R/P364L, and Y486D/other mutations were significantly associated with increased risk of GS, PUCH, and CNS-II, respectively. Total allele number is significantly associated with GS and CNS-II, with each increase in total allele number, the odds ratio (OR) of having GS and CNS-II increased by 1.46 and 4.47 fold, respectively. Having only functional polymorphisms in UGT1A1 gene is associated with increased risk of PUCH, and GS with OR values of 5.67 (95% CI: 1.52-21.13), and 3.88 (95% CI: 1.02-14.78), respectively. Having only mutation is associated with significantly increased risk of having GS phenotype (OR: 34.00, 95% CI: 4.65-248.37), but not CNS-II. Polymorphism plus mutation had the strongest association with CNS-II with OR value of 64.80 (95% CI: 7.68-546.41), followed by GS (OR: 4.53, 95% CI: 1.08-19.08).We detected 7 novel variants, and quantitatively calculated risks of having specific phenotypes using genetic data. Among Chinese children, G71R and P364L is independently associated with PUCH, A(TA)7TAA is associated with GS, and Y486D or other disease-causing mutations were associated with CNS-II. Multiple alleles were associated with more severe phenotypes. Combined variant of G71R+Y486D is a common occurrence among Chinese children with UCH.

Dataset Information

Analysis of the UGT1A1 Genotype in Hyperbilirubinemia Patients: Differences in Allele Frequency and Distribution.

Publications

Analysis of the <i>UGT1A1</i> Genotype in Hyperbilirubinemia Patients: Differences in Allele Frequency and Distribution.

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