Cargando…
Associations of the SLCO1B1 Polymorphisms With Hepatic Function, Baseline Lipid Levels, and Lipid-lowering Response to Simvastatin in Patients With Hyperlipidemia
Our goal was to examine the associations of the 388A>G and 521T>C polymorphisms in the solute carrier organic anion transporter 1B1 (SLCO1B1) gene with hepatic function, baseline lipid levels, and the lipid-lowering efficiency of simvastatin. We recruited 542 patients with hyperlipidemia. The...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6714829/ https://www.ncbi.nlm.nih.gov/pubmed/30336686 http://dx.doi.org/10.1177/1076029618805863 |
_version_ | 1783447126868492288 |
---|---|
author | Wu, Xiangyu Gong, Chen Weinstock, Justin Cheng, Jun Hu, Shengnan Venners, Scott A. Hsu, Yi-Hsiang Wu, Suwen Zha, Xiangdong Jiang, Shanqun Li, Yong Pan, Faming Xu, Xiping |
author_facet | Wu, Xiangyu Gong, Chen Weinstock, Justin Cheng, Jun Hu, Shengnan Venners, Scott A. Hsu, Yi-Hsiang Wu, Suwen Zha, Xiangdong Jiang, Shanqun Li, Yong Pan, Faming Xu, Xiping |
author_sort | Wu, Xiangyu |
collection | PubMed |
description | Our goal was to examine the associations of the 388A>G and 521T>C polymorphisms in the solute carrier organic anion transporter 1B1 (SLCO1B1) gene with hepatic function, baseline lipid levels, and the lipid-lowering efficiency of simvastatin. We recruited 542 patients with hyperlipidemia. The 388A>G and 521T>C polymorphisms were genotyped. Serum alanine aminotransferase (ALT) and aspartate transaminase (AST), Serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were measured before and after an oral 20-mg dose of simvastatin. Individuals with the 388AA genotype had higher ALT and AST levels than those with the 388AG or 388GG genotypes (P = .037 and P = .002, respectively). Individuals with both the 388AA and the 521TT genotypes had the highest levels of ALT and AST (P = .001 and P = .001, respectively). Moreover, we divided all patients into normal and abnormal subgroups based on elevated ALT and AST values (≥ 40 U/L), participants in the abnormal subgroup had a higher frequency of the 388A/521T haplotype and a lower frequency of the 388G/521T haplotype compared to those in the normal subgroup. In addition, compared to 388G allele and 521C allele carriers, individuals with the 388G allele and 521TT genotype carriers had greater TC and LDL-C reduction in response to simvastatin after 4 weeks of treatment. Our conclusion suggests that the interaction between the SLCO1B1 388A>G and 521T>C polymorphisms could be an important genetic determinant of hepatic function and the therapeutic efficiency of simvastatin in Chinese patients with hyperlipidemia. |
format | Online Article Text |
id | pubmed-6714829 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-67148292019-09-04 Associations of the SLCO1B1 Polymorphisms With Hepatic Function, Baseline Lipid Levels, and Lipid-lowering Response to Simvastatin in Patients With Hyperlipidemia Wu, Xiangyu Gong, Chen Weinstock, Justin Cheng, Jun Hu, Shengnan Venners, Scott A. Hsu, Yi-Hsiang Wu, Suwen Zha, Xiangdong Jiang, Shanqun Li, Yong Pan, Faming Xu, Xiping Clin Appl Thromb Hemost Original Articles Our goal was to examine the associations of the 388A>G and 521T>C polymorphisms in the solute carrier organic anion transporter 1B1 (SLCO1B1) gene with hepatic function, baseline lipid levels, and the lipid-lowering efficiency of simvastatin. We recruited 542 patients with hyperlipidemia. The 388A>G and 521T>C polymorphisms were genotyped. Serum alanine aminotransferase (ALT) and aspartate transaminase (AST), Serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were measured before and after an oral 20-mg dose of simvastatin. Individuals with the 388AA genotype had higher ALT and AST levels than those with the 388AG or 388GG genotypes (P = .037 and P = .002, respectively). Individuals with both the 388AA and the 521TT genotypes had the highest levels of ALT and AST (P = .001 and P = .001, respectively). Moreover, we divided all patients into normal and abnormal subgroups based on elevated ALT and AST values (≥ 40 U/L), participants in the abnormal subgroup had a higher frequency of the 388A/521T haplotype and a lower frequency of the 388G/521T haplotype compared to those in the normal subgroup. In addition, compared to 388G allele and 521C allele carriers, individuals with the 388G allele and 521TT genotype carriers had greater TC and LDL-C reduction in response to simvastatin after 4 weeks of treatment. Our conclusion suggests that the interaction between the SLCO1B1 388A>G and 521T>C polymorphisms could be an important genetic determinant of hepatic function and the therapeutic efficiency of simvastatin in Chinese patients with hyperlipidemia. SAGE Publications 2018-10-18 2018-12 /pmc/articles/PMC6714829/ /pubmed/30336686 http://dx.doi.org/10.1177/1076029618805863 Text en © The Author(s) 2018 http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Original Articles Wu, Xiangyu Gong, Chen Weinstock, Justin Cheng, Jun Hu, Shengnan Venners, Scott A. Hsu, Yi-Hsiang Wu, Suwen Zha, Xiangdong Jiang, Shanqun Li, Yong Pan, Faming Xu, Xiping Associations of the SLCO1B1 Polymorphisms With Hepatic Function, Baseline Lipid Levels, and Lipid-lowering Response to Simvastatin in Patients With Hyperlipidemia |
title | Associations of the SLCO1B1 Polymorphisms With Hepatic Function, Baseline
Lipid Levels, and Lipid-lowering Response to Simvastatin in Patients With
Hyperlipidemia |
title_full | Associations of the SLCO1B1 Polymorphisms With Hepatic Function, Baseline
Lipid Levels, and Lipid-lowering Response to Simvastatin in Patients With
Hyperlipidemia |
title_fullStr | Associations of the SLCO1B1 Polymorphisms With Hepatic Function, Baseline
Lipid Levels, and Lipid-lowering Response to Simvastatin in Patients With
Hyperlipidemia |
title_full_unstemmed | Associations of the SLCO1B1 Polymorphisms With Hepatic Function, Baseline
Lipid Levels, and Lipid-lowering Response to Simvastatin in Patients With
Hyperlipidemia |
title_short | Associations of the SLCO1B1 Polymorphisms With Hepatic Function, Baseline
Lipid Levels, and Lipid-lowering Response to Simvastatin in Patients With
Hyperlipidemia |
title_sort | associations of the slco1b1 polymorphisms with hepatic function, baseline
lipid levels, and lipid-lowering response to simvastatin in patients with
hyperlipidemia |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6714829/ https://www.ncbi.nlm.nih.gov/pubmed/30336686 http://dx.doi.org/10.1177/1076029618805863 |
work_keys_str_mv | AT wuxiangyu associationsoftheslco1b1polymorphismswithhepaticfunctionbaselinelipidlevelsandlipidloweringresponsetosimvastatininpatientswithhyperlipidemia AT gongchen associationsoftheslco1b1polymorphismswithhepaticfunctionbaselinelipidlevelsandlipidloweringresponsetosimvastatininpatientswithhyperlipidemia AT weinstockjustin associationsoftheslco1b1polymorphismswithhepaticfunctionbaselinelipidlevelsandlipidloweringresponsetosimvastatininpatientswithhyperlipidemia AT chengjun associationsoftheslco1b1polymorphismswithhepaticfunctionbaselinelipidlevelsandlipidloweringresponsetosimvastatininpatientswithhyperlipidemia AT hushengnan associationsoftheslco1b1polymorphismswithhepaticfunctionbaselinelipidlevelsandlipidloweringresponsetosimvastatininpatientswithhyperlipidemia AT vennersscotta associationsoftheslco1b1polymorphismswithhepaticfunctionbaselinelipidlevelsandlipidloweringresponsetosimvastatininpatientswithhyperlipidemia AT hsuyihsiang associationsoftheslco1b1polymorphismswithhepaticfunctionbaselinelipidlevelsandlipidloweringresponsetosimvastatininpatientswithhyperlipidemia AT wusuwen associationsoftheslco1b1polymorphismswithhepaticfunctionbaselinelipidlevelsandlipidloweringresponsetosimvastatininpatientswithhyperlipidemia AT zhaxiangdong associationsoftheslco1b1polymorphismswithhepaticfunctionbaselinelipidlevelsandlipidloweringresponsetosimvastatininpatientswithhyperlipidemia AT jiangshanqun associationsoftheslco1b1polymorphismswithhepaticfunctionbaselinelipidlevelsandlipidloweringresponsetosimvastatininpatientswithhyperlipidemia AT liyong associationsoftheslco1b1polymorphismswithhepaticfunctionbaselinelipidlevelsandlipidloweringresponsetosimvastatininpatientswithhyperlipidemia AT panfaming associationsoftheslco1b1polymorphismswithhepaticfunctionbaselinelipidlevelsandlipidloweringresponsetosimvastatininpatientswithhyperlipidemia AT xuxiping associationsoftheslco1b1polymorphismswithhepaticfunctionbaselinelipidlevelsandlipidloweringresponsetosimvastatininpatientswithhyperlipidemia |