Carotid plaque and candidate genes related to inflammation and endothelial function in hispanics from Northern Manhattan

Background and Purpose- The genetic influence on carotid atherosclerotic plaque is mostly unknown. This study examines the association between carotid plaque and single nucleotide polymorphisms in selected genes implicated in inflammation and endothelial function. Methods- A total of 43 genes (197 single nucleotide polymorphisms) involved in inflammation and endothelial function were interrogated in 287 Dominicans from the Northern Manhattan Study (mean age, 64±7 years; 58% women) who had undergone high-resolution B-mode ultrasound for examination of carotid plaque. Using an additive genetic model, multiple logistic regression analyses were conducted, a within-gene haplotype analysis was performed, and interactions between genes were examined. Results were validated in an independent set of 301 Dominicans. Results- Carotid plaque was present in 143 (47%) participants. Nine genes had at least 1 single nucleotide polymorphism associated (P≤0.01) with carotid plaque phenotypes: TNF, NOS2A, IL6R, TNFSF4, PPARA, IL1A, TLR4, ITGA2, and HABP2. Single nucleotide polymorphisms in TNFSF4, PPARA, TLR4, ITGA2, and HABP2 were also implicated with the same carotid phenotype in the validation analysis. Haplotype analysis revealed an additional gene of interest, VCAM1. Conclusions- We report novel associations between variations in 10 genes involved in inflammation and endothelial function and carotid plaque phenotypes in a Dominican sample, with replication for 5 genes in an independent Dominican sample.