Significant associations of the rs2943634 (2q36.3) genetic polymorphism with adiponectin, high density lipoprotein cholesterol and ischemic stroke.

BACKGROUND: rs2943634 C/A single nucleotide polymorphism (SNP), located in a non coding region of chromosome 2q36.3, has been associated with coronary artery disease in two genome wide association studies. Our goal was to investigate its relation with myocardial infarction (MI) and ischemic stroke (IS), as well as with 12 intermediate risk phenotypes, in a population-based prospective cohort study.

METHODS: rs2943634 was genotyped in a case-cohort study including a random sample of 1891 individuals (subcohort) and all incident MI (n=211) and IS (n=144) cases during a mean follow-up of 8.2±2.2years, nested within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort comprising 27,548 middle-aged men and women.

RESULTS: rs2943634 minor allele (A) was associated in an additive fashion with lower risk of IS but not with MI [hazard ratio (HR)=0.66; 95% confidence interval (CI): 0.50-0.87; P=0.003; HR=1.02; 95% CI: 0.82-1.28; P=0.83 respectively, for the age and sex adjusted model]. Furthermore, it was related to slightly higher levels of plasma adiponectin [CC 6.94, CA 7.27, AA 7.86μg/ml, P=0.0002] and high density lipoprotein (HDL)-cholesterol (CC 52.08, CA 53.05 and AA 55.27mg/dl, P=0.002), based on additive models. Adjustment for adiponectin and HDL-cholesterol did not attenuate the association between the SNP and IS risk. In contrast, adjustment for adiponectin abolished the association between the SNP and HDL-cholesterol and adjustment for HDL-cholesterol attenuated the association between the SNP and adiponectin.

CONCLUSIONS: Our findings suggest that rs2943634 is associated with IS risk and with plasma levels of HDL-cholesterol and adiponectin in this German population. Further investigations are needed to confirm these results and to clarify the mechanisms underlying the association.