A genetic variant on chromosome 9p21 and incident heart failure in the ARIC study

Aims: Recent studies showed that polymorphisms on chromosome 9p21 are associated with coronary heart disease (CHD), but few studies examined the association with heart failure (HF), stroke, or other subclinical atherosclerotic diseases. We tested the association of chromosome 9p21 polymorphisms with non-coronary atherosclerotic diseases.Methods and resultsWe studied 4018 African-American and 11 085 white participants from the Atherosclerosis Risk in Communities Study, aged 45-64 at baseline (1987-89). We examined associations of rs10757274 and rs2383206 polymorphisms with incident HF through 2005 and ischaemic stroke through 2004, and with prevalent carotid atherosclerosis and peripheral artery disease (PAD) at baseline. The GG genotype of rs10757274 was associated with increased HF risk for whites. This association seemed independent of the established link between rs10757274 and clinical CHD, although an impact of rs10757274 on subclinical CHD leading to HF is not eliminated. Among whites, GG homozygotes were at weakly increased carotid atherosclerosis risk. There seemed to be no associations for ischaemic stroke or PAD. The results were essentially similar for rs2383206.ConclusionThe GG genotype of rs10757274 on chromosome 9p21, which has been shown to increase CHD risk, is also associated with increased HF risk among whites. It is weakly or not associated with several other atherosclerosis outcomes.