Published online before print June 23, 2009, doi: 10.1161/CIRCGENETICS.108.825935
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Original Articles |
The 9p21 Myocardial Infarction Risk Allele Increases Risk of Peripheral Artery Disease in Older People
From the Peninsula Medical School (C.C., N.R., W.H., T.M.F., A.M., D.M.), Exeter, United Kingdom; Department of Medicine (M.M.M.), Northwestern University’s Feinberg School of Medicine, Chicago, Ill; National Institute on Aging/National Institutes of Health (D.M.), Baltimore, Md; Longitudinal Studies Section (L.F.), Clinical Research Branch, Gerontology Research Center, National Institute on Aging, Baltimore, Md; Geriatric Unit (S.B.), Azienda Sanitaria di Firenze, Florence, Italy; Department of Epidemiology (I.M., J.M.Z.), Graduate School of Public Health University of Pittsburgh, Pittsburgh, Pa; Department of Preventive Medicine and Center for Genomics and Bioinformatics (R.L), College of Medicine, University of Tennessee Health Science Center, Memphis, Tenn; San Francisco Coordinating Center (G.T.), California Pacific Medical Center Research Institute, San Francisco, Calif; and Laboratory of Epidemiology (J.G., T.H.), Demography and Biometry, National Institute on Aging, Bethesda, Md.
Correspondence to David Melzer, PhD, Epidemiology and Public Health Group, Peninsula Medical School, RD&E Wonford Site, Barrack Road, Exeter, Devon EX2 5DW, United Kingdom. E-mail david.melzer{at}pms.ac.uk
Received October 6, 2008; accepted May 11, 2009.
Background— A common variant at chromosome 9p21 (tagged by the rs1333049 or rs10757278 single-nucleotide polymorphism) is strongly associated with myocardial infarction and major arterial aneurysms. An association with peripheral arterial disease (PAD) was also reported in a sample younger than 75 years, but this disappeared on removal of respondents with a myocardial infarction history, resulting in an odds ratio of 1.09 for PAD (P=0.075). We aimed at estimating the association of this variant with an Ankle-Brachial Index (ABI) and PAD in 3 older populations.
Methods and Results— We used data from the InCHIANTI, Baltimore Longitudinal Study of Aging, and Health, Aging, and Body Composition studies. In 2630 white individuals (mean age, 76.4 years), the C allele at rs1333049 was associated with lower mean ABI measures and with an increased prevalence of PAD. These associations remained after removal of baseline and incident myocardial infarction cases over a 6-year follow-up for both ABI (–0.017 ABI units; 95% CI, –0.03 to –0.01; P=1.3x10–4) and PAD (per allele odds ratio, 1.29; 95% CI, 1.06 to 1.56; P=0.012). These associations also remained after adjustment for known atherosclerosis risk factors, including diabetes mellitus, smoking, hypercholesterolemia, and hypertension.
Conclusions— The C allele at rs1333049 is associated with an increased prevalence of PAD and lower mean ABI. This association was independent of the presence of diagnosed myocardial infarction and atherosclerotic risk factors in 3 older white populations.
Key Words: genetics • myocardial infarction • peripheral vascular disease • 9p21 • CDKN2a/2b