Abstract
A low level of HDL-C is the most common plasma lipid abnormality observed in men with established coronary heart disease (CHD). To identify allelic variants associated with susceptibility to low HDL-C and CHD, we examined 60 candidate genes with key roles in HDL metabolism, insulin resistance, and inflammation using samples from the Veterans Affairs HDL Intervention Trial (VA-HIT; cases, n = 699) and the Framingham Offspring Study (FOS; controls, n = 705). VA-HIT was designed to examine the benefits of HDL-raising with gemfibrozil in men with low HDL-C (≤40 mg/dl) and established CHD. After adjustment for multiple testing within each gene, single-nucleotide polymorphisms (SNP) significantly associated with case status were identified in the genes encoding LIPC (rs4775065, P < 0.0001); CETP (rs5882, P = 0.0002); RXRA (rs11185660, P = 0.0021); ABCA1 (rs2249891, P = 0.0126); ABCC6 (rs150468, P = 0.0206; rs212077, P = 0.0443); CUBN (rs7893395, P = 0.0246); APOA2 (rs3813627, P = 0.0324); SELP (rs732314, P = 0.0376); and APOC4 (rs10413089, P = 0.0425). Included among the novel findings of this study are the identification of susceptibility alleles for low HDL-C/CHD risk in the genes encoding CUBN and RXRA, and the observation that genetic variation in SELP may influence CHD risk through its effects on HDL.
Highlights
A low level of high density lipoprotein cholesterol (HDL-C) is the most common plasma lipid abnormality observed in men with established coronary heart disease (CHD)
50% of men with CHD have a low level of HDL-C, and not elevated low density lipoprotein cholesterol (LDLC), as their primary lipid abnormality [5]
To identify susceptibility loci for the low HDL-C/CHD trait, we examined the allelic variation of 1,114 singlenucleotide polymorphisms (SNP) in 60 candidate genes using cases from Veterans Affairs HDL Intervention Trial (VA-HIT) before treatment and controls selected from the Framingham Offspring Study (FOS)
Summary
A low level of HDL-C is the most common plasma lipid abnormality observed in men with established coronary heart disease (CHD). Included among the novel findings of this study are the identification of susceptibility alleles for low HDL-C/CHD risk in the genes encoding CUBN and RXRA, and the observation that genetic variation in SELP may influence CHD risk through its effects on HDL.—Peloso, G. Common genetic variation in multiple metabolic pathways influences susceptibility to low HDL-cholesterol and coronary heart disease. 50% of men with CHD have a low level of HDL-C, and not elevated low density lipoprotein cholesterol (LDLC), as their primary lipid abnormality [5].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
