European Heart Journal Advance Access originally published online on March 26, 2009
European Heart Journal 2009 30(10):1222-1228; doi:10.1093/eurheartj/ehp087
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A genetic variant on chromosome 9p21 and incident heart failure in the ARIC study
1 Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, 1300 S Second Street, Suite 300, Minneapolis, MN 55454-1015, USA
2 Department of Public Health Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
3 Department of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, NC, USA
4 Human Genetics Center and Institute for Molecular Medicine, University of Texas Health Science Center, Houston, TX, USA
Received 27 June 2008; revised 5 February 2009; accepted 18 February 2009; online publish-ahead-of-print 26 March 2009.
* Corresponding author. Tel: +1 612 626 8862, Fax: +1 612 624 0315, Email: folso001{at}umn.edu
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 results: We 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.
Conclusion: The 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.
Key Words: Epidemiology • Cohort study • Genetics • Congestive heart failure • Atherosclerosis