| Gender, but not CYP7A1 or SLCO1B1 Polymorphism, Affects the Fasting Plasma Concentrations of Bile Acids in Human Beings. | |
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MedLine Citation:
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PMID: 21902813 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Cholesterol 7α-hydroxylase (CYP7A1) is the rate-limiting enzyme of bile acid production in human beings, and organic anion transporting polypeptide 1B1 (OATP1B1) may influence bile acid hepatic uptake and cholesterol and bile acid synthesis rate. Our purpose was to investigate the effects of gender and CYP7A1 and SLCO1B1 polymorphisms on the fasting plasma concentrations of bile acids, bile acid synthesis marker and total cholesterol in a Finnish population. Fasting plasma concentrations of 16 endogenous bile acids, their synthesis marker (7α-hydroxy-4-cholesten-3-one) and total cholesterol were measured in 243 samples from 143 healthy volunteers. The volunteers were genotyped for 6 haplotype-tagging single nucleotide polymorphisms (SNPs) of CYP7A1 and two functionally relevant SNPs in SLCO1B1. The mean plasma concentrations of chenodeoxycholic acid, glycochenodeoxycholic acid, ursodeoxycholic acid and glycoursodeoxycholic acid were 61% to 111% higher in men than in women (P≤0.001). Accordingly, the mean concentration of total bile acids was 51% higher in men than in women (P=0.001). The CYP7A1 rs8192879 and rs1023652 SNPs were associated with deoxycholic acid and hyodeoxycholic acid concentrations, respectively, but the associations were not significant after correction for multiple testing. None of the six CYP7A1 SNPs was associated with the plasma concentrations of cholesterol or 7α-hydroxy-4-cholesten-3-one. SLCO1B1 genotype was associated with total plasma cholesterol concentration only, but the association was not significant after correction for multiple testing. In general, the gender contributes substantially more to variation in fasting plasma bile acid concentrations than CYP7A1 or SLCO1B1 polymorphism do. Common genetic variability in CYP7A1 is unlikely to play a significant role in cholesterol metabolism and bile acid homeostasis under normal physiological conditions. |
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Authors:
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Xiaoqiang Xiang; Janne T Backman; Pertti J Neuvonen; Mikko Niemi |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-9-8 |
Journal Detail:
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Title: Basic & clinical pharmacology & toxicology Volume: - ISSN: 1742-7843 ISO Abbreviation: - Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-9-9 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101208422 Medline TA: Basic Clin Pharmacol Toxicol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society. |
Affiliation:
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Department of Clinical Pharmacology, University of Helsinki and HUSLAB, Helsinki University Central Hospital, Helsinki, Finland. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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