The 9p21 myocardial infarction risk allele increases risk of peripheral artery disease in older people

Christie Cluett, Mary McGrae McDermott, Jack Guralnik, Luigi Ferrucci, Stefania Bandinelli, Iva Miljkovic, Joseph M. Zmuda, Rongling Li, Greg Tranah, Tamara Harris, Neil Rice, William Henley, Timothy M. Frayling, Anna Murray, David Melzer

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)347-353
Number of pages7
JournalCirculation: Cardiovascular Genetics
Volume2
Issue number4
DOIs
StatePublished - Aug 2009
Externally publishedYes

Fingerprint

Peripheral Arterial Disease
Ankle Brachial Index
Alleles
Myocardial Infarction
Odds Ratio
Baltimore
Body Composition
Hypercholesterolemia
Population
Aneurysm
Single Nucleotide Polymorphism
Longitudinal Studies
Atherosclerosis
Diabetes Mellitus
Chromosomes
Smoking
Hypertension
Health

Keywords

  • 9p21
  • CDKN2a/2b
  • Genetics
  • Myocardial infarction
  • Peripheral vascular disease

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)
  • Genetics
  • Medicine(all)

Cite this

Cluett, C., McDermott, M. M., Guralnik, J., Ferrucci, L., Bandinelli, S., Miljkovic, I., ... Melzer, D. (2009). The 9p21 myocardial infarction risk allele increases risk of peripheral artery disease in older people. Circulation: Cardiovascular Genetics, 2(4), 347-353. https://doi.org/10.1161/CIRCGENETICS.108.825935

The 9p21 myocardial infarction risk allele increases risk of peripheral artery disease in older people. / Cluett, Christie; McDermott, Mary McGrae; Guralnik, Jack; Ferrucci, Luigi; Bandinelli, Stefania; Miljkovic, Iva; Zmuda, Joseph M.; Li, Rongling; Tranah, Greg; Harris, Tamara; Rice, Neil; Henley, William; Frayling, Timothy M.; Murray, Anna; Melzer, David.

In: Circulation: Cardiovascular Genetics, Vol. 2, No. 4, 08.2009, p. 347-353.

Research output: Contribution to journalArticle

Cluett, C, McDermott, MM, Guralnik, J, Ferrucci, L, Bandinelli, S, Miljkovic, I, Zmuda, JM, Li, R, Tranah, G, Harris, T, Rice, N, Henley, W, Frayling, TM, Murray, A & Melzer, D 2009, 'The 9p21 myocardial infarction risk allele increases risk of peripheral artery disease in older people', Circulation: Cardiovascular Genetics, vol. 2, no. 4, pp. 347-353. https://doi.org/10.1161/CIRCGENETICS.108.825935
Cluett, Christie ; McDermott, Mary McGrae ; Guralnik, Jack ; Ferrucci, Luigi ; Bandinelli, Stefania ; Miljkovic, Iva ; Zmuda, Joseph M. ; Li, Rongling ; Tranah, Greg ; Harris, Tamara ; Rice, Neil ; Henley, William ; Frayling, Timothy M. ; Murray, Anna ; Melzer, David. / The 9p21 myocardial infarction risk allele increases risk of peripheral artery disease in older people. In: Circulation: Cardiovascular Genetics. 2009 ; Vol. 2, No. 4. pp. 347-353.
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abstract = "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.",
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AU - Cluett, Christie

AU - McDermott, Mary McGrae

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

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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.

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