Relationship of HDL and coronary heart disease to a common amino acid polymorphism in the cholesteryl ester transfer protein in men with and without hypertriglyceridemia

Abstract

Plasma triglyceride (TG) levels are inversely related to HDL-cholesterol levels and subjects with high TG and low HDL cholesterol have increased coronary heart disease (CHD) risk. Plasma cholesteryl ester transfer protein (CETP) transfers cholesteryl esters from HDL to TG-rich lipoproteins. In this study we determined the relationship between a common CETP amino acid polymorphism (I405V) and CETP and HDL levels and CHD prevalence in 576 men of Japanese ancestry in the Honolulu Heart Program cohort. This conservative substitution was associated with altered plasma CETP concentration (1.95 ؎ 0.54, 1.91 ؎ 0.57, and 1.77 ؎ 0.57 g/ml for the II , IV and VV genotypes, respectively). The distribution of plasma CETP concentrations among the VV , but not II , men appeared bimodal ( P Ͻ 0.01), suggesting the presence of a functionally significant CETP gene mutation(s) in a subset of V alleles. HDL-C levels were higher in VV than IV for II men (55.4 ؎ 17.4, 51.3 ؎ 16.6, 51.1 ؎ 17.0 mg/dl, P Ͻ 0.04). However, the increase in HDL was only significant in VV men with plasma TG Ͼ 165 mg/dl. Although CHD prevalence was not significantly different among the three genotypes in this population, in the subpopulation with high plasma TG, CHD prevalence appeared higher among VV than IV or II subjects (38% vs. 27% vs. 18%, P Ͻ 0.05 for an interaction of genotype and plasma TG levels). In fresh plasma from a separate group of normolipidemic subjects, the V/I polymorphism was not associated with any change in plasma CETP specific activity.The data suggest that a widespread and common CETP gene mutation(s) in linkage disequilibrium with 405V causes low CETP. Among hypertriglyceridemic men this is associated with higher HDL and possibly with increased CHD.-Bruce, C., D. S. Sharp, and A. R. Tall. Relationship of HDL and coronary heart disease to a common amino acid polymorphism in the cholesteryl ester transfer protein in men with and without hypertriglyceridemia.

Association Between Renal Function and Cognitive Ability Domains in the Einstein Aging Study: A Cross-Sectional Analysis

“…This was measured using the 15-item Geriatric Depression Scale (29), with scores ≥6 indicating clinically significant depressive symptoms. Genetic confounders included apolioprotein E allele e4, known for its association with Alzheimer's disease (30), and cholesterylester transfer protein (CETP) with the I/V or V/V genotype, known for its association with longevity and in patients with hypertriglyceridemia, and coronary heart disease (31,32). These genes may mediate any associations between cognition and renal function.…”

The cholesteryl ester transfer protein I405V polymorphism is associated with increased high-density lipoprotein levels and decreased risk of myocardial infarction: the Rotterdam Study

“…The relationship with coronary heart disease (CHD) is less well understood; previous studies reported discordant results [3,6]. To further elucidate the role of the I405V polymorphism in CHD, this study examined its association with lipids, common carotid intima-media thickness (IMT) and plaques, and incidence of myocardial infarction (MI) in a population-based cohort in Rotterdam, The Netherlands.…”

“…The CETP I405V (rs5882) polymorphism, located in a known binding domain [2], causes an isoleucine/valine shift, leading to decreased protein levels [3]. The impact of this polymorphism on HDL levels was clearly established in a recent meta-analysis [4].…”

Συσχετισμός Των Γονιδίων Της Λιποπρωτεϊνικής Λιπάσης, Της Απολιποπρωτεΐνης CIII Και Της Πρωτεΐνης Μεταφοράς Εστέρων Χοληστερόλης Με Τη Μεταγευματική Λιπαιμία

“…Ωστόσο, δεν υπάρχει συμφωνία ανάμεσα σε όλες τις μελέτες για την αθηρογόνο δράση του Β1. Παραδόξως, υπάρχουν μελέτες που αναφέρουν ότι ο καρδιαγγειακός κίνδυνος είναι αυξημένος στους Β2 φορείς (Bruce et al, 1998b;Agerholm-Larsen et al, 2000;Borggreve et al, 2006). Αντίθετα, μία μετα-ανάλυση 7 χωρών παρατήρησε χαμηλότερο καρδιαγγειακό κίνδυνο στους ομόζυγους Β2 συγκριτικά με τους ομόζυγους Β1 (Boekholdt et al, 2005).…”