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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...

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Autores principales: 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
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
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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.
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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
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