The 9p21 locus interacts with obesity to increase atherosclerotic burden

Purpose: Although the rs1333049 common variant on chromosome 9p21 confers a major risk for\natherosclerosis-related phenotypes, whether it interacts with cardiovascular risk factors to determine the\natherosclerotic burden is yet unknown.\nMethods: We genotyped rs1333049 in the population-based, prospective Asklepios Study of 2,481 healthy\nindividuals, in which subclinical atherosclerotic lesions were measured in all 4 carotid and femoral arteries\nby ultrasound.\nResults: The at-risk C-allele was significantly and independently associated with atherosclerosis in single\ncarotid and femoral arteries, and increased successively the risk for plaques in 1, 2, 3 or 4 vessels\n(P=0.011). Remarkably, rs1333049 interacted with obesity (P=0.019 for interaction), but not with other\ncardiovascular risk factors. Concomitantly, the odds ratios of the C-allele for prevalent plaque increased\ngradually per increasing number of affected vessels in obese individuals (P=0.006), whereas no such\neffects were seen in non-obese (P=0.35) (Table 1). A similar interaction was noticed with intima-media\nthickness (IMT), with rs1333049 increasing IMT only in obese.\nConclusions: We report that 9p21 is strongly associated with the atherosclerotic burden in obese, but not\nin lean individuals. With prevalence of obesity increasing rapidly, this association is of major importance to\npredict risk of cardiovascular disease.