Cargando…

Combined Effects of UGT1A1 and SLCO1B1 Variants on Chinese Adult Mild Unconjugated Hyperbilirubinemia

The potential for genetic variation to cause adult unconjugated hyperbilirubinemia is increasingly being recognized. However, the cumulative effects of genetic variants have not been fully illuminated. The current study aimed to investigate the effects of uridine diphospho-glucuronosyl transferase 1...

Descripción completa

Detalles Bibliográficos
Autores principales: Bai, Jie, Luo, Lei, Liu, Shuang, Liang, Chen, Bai, Li, Chen, Yu, Zheng, Sujun, Duan, Zhongping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834774/
https://www.ncbi.nlm.nih.gov/pubmed/31737051
http://dx.doi.org/10.3389/fgene.2019.01073
_version_ 1783466549093335040
author Bai, Jie
Luo, Lei
Liu, Shuang
Liang, Chen
Bai, Li
Chen, Yu
Zheng, Sujun
Duan, Zhongping
author_facet Bai, Jie
Luo, Lei
Liu, Shuang
Liang, Chen
Bai, Li
Chen, Yu
Zheng, Sujun
Duan, Zhongping
author_sort Bai, Jie
collection PubMed
description The potential for genetic variation to cause adult unconjugated hyperbilirubinemia is increasingly being recognized. However, the cumulative effects of genetic variants have not been fully illuminated. The current study aimed to investigate the effects of uridine diphospho-glucuronosyl transferase 1A1 (UGT1A1) and/or solute carrier organic anion transporter family member 1B (SLCO1B) polymorphic variants and their combined effects on mild unconjugated hyperbilirubinemia in Chinese adults. Fourteen genetic variants in the UGT1A1 or SLCO1B gene were genotyped through sequencing in 148 adults with unconjugated hyperbilirubinemia and 158 healthy controls. Variants c.-3275T > G, (TA)(6)>(TA)(7), c.211G > A or c.1091C > T within the UGT1A1 gene as well as c.521T > C within the SLCO1B1 gene appear to be genetic risk factors for inherited unconjugated hyperbilirubinemia. After adjusting for covariates, the results of multivariate logistic regressions revealed that odds ratios (ORs) [(with 95% confidence interval (CI)] of these five variants were 2.35 (95% CI: 1.37–4.01, p = 0.002), 2.38 (95% CI: 1.35–4.20, p = 0.003), 2.99 (95% CI: 1.71–5.21, p < 0.001), 7.60 (95% CI: 1.99–28.96, p = 0.003), and 2.54 (95% CI: 1.27–5.11, p = 0.009), respectively. The OR for unconjugated hyperbilirubinemia is positively correlated with the cumulative number of these five variants in adults. And the greater the number of genetic variations, the higher the total bilirubin level. Adults carrying diplotype 3/4 (homozygous c.-3275T > G and heterozygous (TA)(6)>(TA)(7)) had higher bilirubin levels than those with diplotypes 1/3 (heterozygous c.-3275T > G and (TA)(6)>(TA)(7))) or 1/4 (heterozygous c.-3275T > G) (P < 0.05). Similarly, bilirubin levels in individuals with diplotype 2/4 (heterozygous c.-3275T > G and c.211G > A) were higher than adults carrying diplotypes 1/2 (heterozygous c.211G > A) or 1/4 (P < 0.001). For subjects with heterozygous or homozygous variant c.211G> A, as the number of c.521T > C alleles variation increased, the incidence of unconjugated hyperbilirubinemia increased, but it was not statistically significant. Our results indicate that variants of UGT1A1 and/or SLCO1B1 have combined effects on Chinese adult mild unconjugated hyperbilirubinemia.
format Online
Article
Text
id pubmed-6834774
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-68347742019-11-15 Combined Effects of UGT1A1 and SLCO1B1 Variants on Chinese Adult Mild Unconjugated Hyperbilirubinemia Bai, Jie Luo, Lei Liu, Shuang Liang, Chen Bai, Li Chen, Yu Zheng, Sujun Duan, Zhongping Front Genet Genetics The potential for genetic variation to cause adult unconjugated hyperbilirubinemia is increasingly being recognized. However, the cumulative effects of genetic variants have not been fully illuminated. The current study aimed to investigate the effects of uridine diphospho-glucuronosyl transferase 1A1 (UGT1A1) and/or solute carrier organic anion transporter family member 1B (SLCO1B) polymorphic variants and their combined effects on mild unconjugated hyperbilirubinemia in Chinese adults. Fourteen genetic variants in the UGT1A1 or SLCO1B gene were genotyped through sequencing in 148 adults with unconjugated hyperbilirubinemia and 158 healthy controls. Variants c.-3275T > G, (TA)(6)>(TA)(7), c.211G > A or c.1091C > T within the UGT1A1 gene as well as c.521T > C within the SLCO1B1 gene appear to be genetic risk factors for inherited unconjugated hyperbilirubinemia. After adjusting for covariates, the results of multivariate logistic regressions revealed that odds ratios (ORs) [(with 95% confidence interval (CI)] of these five variants were 2.35 (95% CI: 1.37–4.01, p = 0.002), 2.38 (95% CI: 1.35–4.20, p = 0.003), 2.99 (95% CI: 1.71–5.21, p < 0.001), 7.60 (95% CI: 1.99–28.96, p = 0.003), and 2.54 (95% CI: 1.27–5.11, p = 0.009), respectively. The OR for unconjugated hyperbilirubinemia is positively correlated with the cumulative number of these five variants in adults. And the greater the number of genetic variations, the higher the total bilirubin level. Adults carrying diplotype 3/4 (homozygous c.-3275T > G and heterozygous (TA)(6)>(TA)(7)) had higher bilirubin levels than those with diplotypes 1/3 (heterozygous c.-3275T > G and (TA)(6)>(TA)(7))) or 1/4 (heterozygous c.-3275T > G) (P < 0.05). Similarly, bilirubin levels in individuals with diplotype 2/4 (heterozygous c.-3275T > G and c.211G > A) were higher than adults carrying diplotypes 1/2 (heterozygous c.211G > A) or 1/4 (P < 0.001). For subjects with heterozygous or homozygous variant c.211G> A, as the number of c.521T > C alleles variation increased, the incidence of unconjugated hyperbilirubinemia increased, but it was not statistically significant. Our results indicate that variants of UGT1A1 and/or SLCO1B1 have combined effects on Chinese adult mild unconjugated hyperbilirubinemia. Frontiers Media S.A. 2019-10-31 /pmc/articles/PMC6834774/ /pubmed/31737051 http://dx.doi.org/10.3389/fgene.2019.01073 Text en Copyright © 2019 Bai, Luo, Liu, Liang, Bai, Chen, Zheng and Duan http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Bai, Jie
Luo, Lei
Liu, Shuang
Liang, Chen
Bai, Li
Chen, Yu
Zheng, Sujun
Duan, Zhongping
Combined Effects of UGT1A1 and SLCO1B1 Variants on Chinese Adult Mild Unconjugated Hyperbilirubinemia
title Combined Effects of UGT1A1 and SLCO1B1 Variants on Chinese Adult Mild Unconjugated Hyperbilirubinemia
title_full Combined Effects of UGT1A1 and SLCO1B1 Variants on Chinese Adult Mild Unconjugated Hyperbilirubinemia
title_fullStr Combined Effects of UGT1A1 and SLCO1B1 Variants on Chinese Adult Mild Unconjugated Hyperbilirubinemia
title_full_unstemmed Combined Effects of UGT1A1 and SLCO1B1 Variants on Chinese Adult Mild Unconjugated Hyperbilirubinemia
title_short Combined Effects of UGT1A1 and SLCO1B1 Variants on Chinese Adult Mild Unconjugated Hyperbilirubinemia
title_sort combined effects of ugt1a1 and slco1b1 variants on chinese adult mild unconjugated hyperbilirubinemia
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834774/
https://www.ncbi.nlm.nih.gov/pubmed/31737051
http://dx.doi.org/10.3389/fgene.2019.01073
work_keys_str_mv AT baijie combinedeffectsofugt1a1andslco1b1variantsonchineseadultmildunconjugatedhyperbilirubinemia
AT luolei combinedeffectsofugt1a1andslco1b1variantsonchineseadultmildunconjugatedhyperbilirubinemia
AT liushuang combinedeffectsofugt1a1andslco1b1variantsonchineseadultmildunconjugatedhyperbilirubinemia
AT liangchen combinedeffectsofugt1a1andslco1b1variantsonchineseadultmildunconjugatedhyperbilirubinemia
AT baili combinedeffectsofugt1a1andslco1b1variantsonchineseadultmildunconjugatedhyperbilirubinemia
AT chenyu combinedeffectsofugt1a1andslco1b1variantsonchineseadultmildunconjugatedhyperbilirubinemia
AT zhengsujun combinedeffectsofugt1a1andslco1b1variantsonchineseadultmildunconjugatedhyperbilirubinemia
AT duanzhongping combinedeffectsofugt1a1andslco1b1variantsonchineseadultmildunconjugatedhyperbilirubinemia