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Effects of SLCO1B1 Genetic Variant on Metabolite Profile in Participants on Simvastatin Treatment

Organic-anion-transporting polypeptide 1B1 (OATP1B1), encoded by the solute carrier organic anion transporter family member 1B1 gene (SLCO1B1), is highly expressed in the liver and transports several endogenous metabolites into the liver, including statins. Previous studies have not investigated the...

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Autores principales: Fernandes Silva, Lilian, Ravi, Rowmika, Vangipurapu, Jagadish, Oravilahti, Anniina, Laakso, Markku
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9785662/
https://www.ncbi.nlm.nih.gov/pubmed/36557197
http://dx.doi.org/10.3390/metabo12121159
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author Fernandes Silva, Lilian
Ravi, Rowmika
Vangipurapu, Jagadish
Oravilahti, Anniina
Laakso, Markku
author_facet Fernandes Silva, Lilian
Ravi, Rowmika
Vangipurapu, Jagadish
Oravilahti, Anniina
Laakso, Markku
author_sort Fernandes Silva, Lilian
collection PubMed
description Organic-anion-transporting polypeptide 1B1 (OATP1B1), encoded by the solute carrier organic anion transporter family member 1B1 gene (SLCO1B1), is highly expressed in the liver and transports several endogenous metabolites into the liver, including statins. Previous studies have not investigated the association of SLCO1B1 rs4149056 variant with the risk of type 2 diabetes (T2D) or determined the metabolite signature of the C allele of SLCO1B1 rs4149056 (SLCO1B1 rs4149056-C allele) in a large randomly selected population. SLCO1B1 rs4149056-C inhibits OATP1B1 transporter and is associated with increased levels of blood simvastatin concentrations. Our study is to first to show that SLCO1B1 rs4149056 variant is not significantly associated with the risk of T2D, suggesting that simvastatin has a direct effect on the risk of T2D. Additionally, we investigated the effects of SLCO1B1 rs4149056-C on plasma metabolite concentrations in 1373 participants on simvastatin treatment and in 1368 age- and body-mass index (BMI)-matched participants without any statin treatment. We found 31 novel metabolites significantly associated with SLCO1B1 rs4149056-C in the participants on simvastatin treatment and in the participants without statin treatment. Simvastatin decreased concentrations of dicarboxylic acids, such as docosadioate and dodecanedioate, that may increase beta- and peroxisomal oxidation and increased the turnover of cholesterol into bile acids, resulting in a decrease in steroidogenesis due to limited availability of cholesterol for steroid synthesis. Our findings suggest that simvastatin exerts its effects on the lowering of low-density lipoprotein (LDL) cholesterol concentrations through several distinct pathways in the carriers of SLCO1B1 rs4149056-C, including dicarboxylic acids, bile acids, steroids, and glycerophospholipids.
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spelling pubmed-97856622022-12-24 Effects of SLCO1B1 Genetic Variant on Metabolite Profile in Participants on Simvastatin Treatment Fernandes Silva, Lilian Ravi, Rowmika Vangipurapu, Jagadish Oravilahti, Anniina Laakso, Markku Metabolites Article Organic-anion-transporting polypeptide 1B1 (OATP1B1), encoded by the solute carrier organic anion transporter family member 1B1 gene (SLCO1B1), is highly expressed in the liver and transports several endogenous metabolites into the liver, including statins. Previous studies have not investigated the association of SLCO1B1 rs4149056 variant with the risk of type 2 diabetes (T2D) or determined the metabolite signature of the C allele of SLCO1B1 rs4149056 (SLCO1B1 rs4149056-C allele) in a large randomly selected population. SLCO1B1 rs4149056-C inhibits OATP1B1 transporter and is associated with increased levels of blood simvastatin concentrations. Our study is to first to show that SLCO1B1 rs4149056 variant is not significantly associated with the risk of T2D, suggesting that simvastatin has a direct effect on the risk of T2D. Additionally, we investigated the effects of SLCO1B1 rs4149056-C on plasma metabolite concentrations in 1373 participants on simvastatin treatment and in 1368 age- and body-mass index (BMI)-matched participants without any statin treatment. We found 31 novel metabolites significantly associated with SLCO1B1 rs4149056-C in the participants on simvastatin treatment and in the participants without statin treatment. Simvastatin decreased concentrations of dicarboxylic acids, such as docosadioate and dodecanedioate, that may increase beta- and peroxisomal oxidation and increased the turnover of cholesterol into bile acids, resulting in a decrease in steroidogenesis due to limited availability of cholesterol for steroid synthesis. Our findings suggest that simvastatin exerts its effects on the lowering of low-density lipoprotein (LDL) cholesterol concentrations through several distinct pathways in the carriers of SLCO1B1 rs4149056-C, including dicarboxylic acids, bile acids, steroids, and glycerophospholipids. MDPI 2022-11-22 /pmc/articles/PMC9785662/ /pubmed/36557197 http://dx.doi.org/10.3390/metabo12121159 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fernandes Silva, Lilian
Ravi, Rowmika
Vangipurapu, Jagadish
Oravilahti, Anniina
Laakso, Markku
Effects of SLCO1B1 Genetic Variant on Metabolite Profile in Participants on Simvastatin Treatment
title Effects of SLCO1B1 Genetic Variant on Metabolite Profile in Participants on Simvastatin Treatment
title_full Effects of SLCO1B1 Genetic Variant on Metabolite Profile in Participants on Simvastatin Treatment
title_fullStr Effects of SLCO1B1 Genetic Variant on Metabolite Profile in Participants on Simvastatin Treatment
title_full_unstemmed Effects of SLCO1B1 Genetic Variant on Metabolite Profile in Participants on Simvastatin Treatment
title_short Effects of SLCO1B1 Genetic Variant on Metabolite Profile in Participants on Simvastatin Treatment
title_sort effects of slco1b1 genetic variant on metabolite profile in participants on simvastatin treatment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9785662/
https://www.ncbi.nlm.nih.gov/pubmed/36557197
http://dx.doi.org/10.3390/metabo12121159
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