文章基本信息

标题：THOC5: a novel gene involved in HDL-cholesterol metabolism
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作者：Maria Keller ; Dorit Schleinitz ; Julia Förster 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2013
卷号：54
期号：11
页码：3170-3176
DOI：10.1194/jlr.M039420
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Although numerous genes are known to regulate serum lipid traits, identified variants explain only a small proportion of the expected heritability. We intended to identify further genetic variants associated with lipid phenotypes in a self-contained population of Sorbs in Germany. We performed a genome-wide association study (GWAS) on LDL-cholesterol, HDL-cholesterol (HDL-C), and triglyceride (TG) levels in 839 Sorbs. All single-nucleotide polymorphisms with a P value P values −5 and confirmed significant effects for 18 previously reported loci. The combined meta-analysis of the three study cohorts (n_(HDL) = 6041; n_(LDL) = 5,995; n_(TG) = 6,087) revealed a novel association for a variant in THOC5 (rs8135828) with serum HDL-C levels ( P = 1.78 × 10⁻⁷; Z -score = −5.221). Consistently, the variant was also associated with circulating APOA1 levels in Sorbs. The small interfering RNA-mediated mRNA silencing of THOC5 in HepG2 cells resulted in lower mRNA levels of APOA1 , SCARB1 , and ABCG8 (all P THOC5 to be a novel gene involved in the regulation of serum HDL-C levels.
关键词：single nucleotide polymorphism ; genome-wide-association study ; mRNA silencing