Abstract 3138: The Effect of Interactions among Variants of CD36 on Hypertensive Heart Disease Phenotypes
Alterations in myocardial metabolism are implicated in mediating hypertensive heart disease (HHD). We hypothesize that variants in CD36 modulate HHD phenotypes both individually and collectively via interactions among CD36 variants and with those in other metabolic regulatory genes. Cardiovascular (CV) phenotypes were characterized by echocardiography and carotid artery ultrasonography. The association between race-specific CD36 tagSNPs (r2>0.8) and HHD traits were tested in Caucasian (C, n=608) and African-American (AA, n=228) adults. Association between dependent variables and individual SNPs were tested by regression analysis adjusting for known confounding covariates. Tests for interaction were carried out by first examining within-gene cis-interactions by regression against haplotypes in CD36, followed by exploratory analysis of cross-gene interactions between CD36 and PPARα, PPARγ, and PGC1α using Bayesian network (BNT) analyses. A total of 14 and 52 CD36 SNPs in C and AA, respectively, were evaluated. In C, no significant main effects for individual CD36 SNPs were detected while 3 CD36 haplotypes were associated with LV diastolic function, LV mass, and LV ejection fraction suggesting a role for interaction of cis-acting elements. In AA, 15 individual SNPs and 17 CD36 haplotypes were associated with HHD-related traits. Exploratory BNT analyses including significant haplotypes from the 4 genes identified meaningful gene-gene interactions in both races, highlighting the complex nature of interactions among CD36 and metabolic regulatory genes in the etiology that deserves further investigation.