TY - JOUR
T1 - The 9p21 myocardial infarction risk allele increases risk of peripheral artery disease in older people
AU - Cluett, Christie
AU - McDermott, Mary Mc Grae
AU - Guralnik, Jack
AU - Ferrucci, Luigi
AU - Bandinelli, Stefania
AU - Miljkovic, Iva
AU - Zmuda, Joseph M.
AU - Li, Rongling
AU - Tranah, Greg
AU - Harris, Tamara
AU - Rice, Neil
AU - Henley, William
AU - Frayling, Timothy M.
AU - Murray, Anna
AU - Melzer, David
PY - 2009/8
Y1 - 2009/8
N2 - 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 1.3×10-4) 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.
AB - 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 1.3×10-4) 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.
KW - 9p21
KW - CDKN2a/2b
KW - Genetics
KW - Myocardial infarction
KW - Peripheral vascular disease
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U2 - 10.1161/CIRCGENETICS.108.825935
DO - 10.1161/CIRCGENETICS.108.825935
M3 - Article
C2 - 20031606
AN - SCOPUS:71849099015
VL - 2
SP - 347
EP - 353
JO - Circulation. Genomic and precision medicine
JF - Circulation. Genomic and precision medicine
SN - 2574-8300
IS - 4
ER -