文章基本信息

标题：Linkage and association of phospholipid transfer protein activity to LASS4
本地全文：下载
作者：Elisabeth A. Rosenthal ; James Ronald ; Joseph Rothstein 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：2011
卷号：52
期号：10
页码：1837-1846
DOI：10.1194/jlr.P016576
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Phospholipid transfer protein activity (PLTPa) is associated with insulin levels and has been implicated in atherosclerotic disease in both mice and humans. Variation at the PLTP structural locus on chromosome 20 explains some, but not all, heritable variation in PLTPa. In order to detect quantitative trait loci (QTLs) elsewhere in the genome that affect PLTPa, we performed both oligogenic and single QTL linkage analysis on four large families (n = 227 with phenotype, n = 330 with genotype, n = 462 total), ascertained for familial combined hyperlipidemia. We detected evidence of linkage between PLTPa and chromosome 19p (lod = 3.2) for a single family and chromosome 2q (lod = 2.8) for all families. Inclusion of additional marker and exome sequence data in the analysis refined the linkage signal on chromosome 19 and implicated coding variation in LASS4 , a gene regulated by leptin that is involved in ceramide synthesis. Association between PLTPa and LASS4 variation was replicated in the other three families ( P = 0.02), adjusting for pedigree structure. To our knowledge, this is the first example for which exome data was used in families to identify a complex QTL that is not the structural locus.
关键词：cardiovascular disease ; exome analysis ; linkage analysis ; complex trait