Abstract 1783: Genetic Polymorphisms on Chromosome 9p21 May Have Sex Differential Effect on Carotid Atherosclerosis in Healthy Individuals
Background and Purpose Recent genome-wide association studies of myocardial infarction (MI) have confirmed a novel susceptibility locus on chromosome 9p21.3. Additional studies showed single nucleotide polymorphisms (SNPs) in this locus were also related to intracranial and abdominal aneurysms. Since atherosclerosis is an important underlying mechanism for MI and aneurysm, we investigated whether SNPs in this locus are also related to subclinical atherosclerosis in healthy individuals.
Methods A total of 1097 stroke- and MI- free volunteers with mean age of 52 were enrolled for this study. We measured intimal-medial thickness (IMT) by ultrasonography at plaque-free area of common carotid artery (CCA), bifurcation and internal carotid artery (ICA). Four commonly used tagging SNPs (SNP1– 4) were selected and genotyped by the TagMan method. Multivariate liner regression was used with adjustment for age, sex, hypertension, DM, hypercholesterolemia and smoking status. Haplotype analysis was also performed. In addition, we evaluated sex-specific genetic effect.
Results Genotyping data was in Hardy-Weinberg equilibrium. SNP2– 4 were in strong linkage disequilibrium (LD) with D′≥ 0.98 and the LD between SNP1 and the other three SNPs was relatively lower with D′~0.88. SNP1 and SNP2 were significantly associated IMT with p values ranging from 0.045 to 0.009 depending on the genetic models and carotid segments. Further sex-specific analysis showed that SNP1 and SNP2 were only significant for IMT in men but not in women, while SNP3– 4 remained not significant. The most significant result was from the association between SNP1 and CCA IMT in men (p =0.001), which was also significant even after multiple testing correction. Haplotype analysis did not yield any better results than the results from each SNP.
Conclusions Our results supported the 9p21 region has significant effect on subclinical atherosclerosis, which may be used as a risk marker to identify high risk individuals.