Published Online
on June 23, 2009

A more recent version of this article appeared on August 1, 2009

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Original Article

The 9p21 Myocardial Infarction risk allele increases risk of Peripheral Artery Disease in older people.

Christie Cluett¹; Mary McGrae McDermott²; Jack Guralnik³; Luigi Ferrucci³; Stefania Bandinelli⁴; Iva Miljkovic⁵; Joseph M. Zmuda⁵; Rongling Li⁶; Greg Tranah⁷; Tamara Harris³; Neil Rice¹; William Henley¹; Timothy M. Frayling¹; Anna Murray¹ and David Melzer^1,8

¹ Peninsula Medical School, Exeter, United Kingdom;
² Northwestern University, Chicago, IL;
³ National Institute on Aging, Bethesda, MD;
⁴ Azienda Sanitaria di Firenze, Florence, Italy;
⁵ University of Pittsburgh, Pittsburgh, PA;
⁶ University of Tennessee Health Science Center, Memphis, TN;
⁷ California Pacific Medical Center Research Institute, San Francisco, CA

⁸ E-mail: david.melzer{at}pms.ac.uk

Background—A common variant at chromosome 9p21 (tagged by the rs1333049 or rs10757278 SNP) is strongly associated with Myocardial Infarction (MI) and major arterial aneurysms. An association with Peripheral Arterial Disease (PAD) was also reported in a sample aged <75 years, but this disappeared on removal of respondents with a MI history, resulting in an odds ratio for PAD of 1.09 (p=0.075). We aimed to estimate the association of this variant with Ankle Brachial Index (ABI) and PAD in three older populations.

Methods and Results—We used data from the InCHIANTI, Baltimore Longitudinal Study of Aging and Health, Aging and Body Composition studies. In 2,630 Caucasian individuals (mean age 76.4 years) the C allele at rs1333049 was associated with lower mean ABI measures and with increased prevalence of PAD. These associations remained after removal of baseline and incident MI cases over a 6 year follow-up for both ABI (-0.017 ABI units, 95% CI: -0.03- -0.01, p=1.3x10^-4) and PAD (per allele OR: 1.29, 95% CI: 1.06-1.56, 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 Peripheral Arterial Disease and lower mean Ankle Brachial Index. This association was independent of the presence of diagnosed MI and atherosclerotic risk factors in 3 older Caucasian populations.

Key Words: genetics • myocardial infarction • peripheral vascular disease • 9p21 • CDKN2a/2b