Genetic variation at the 9p21 locus predicts angiographic coronary artery disease prevalence but not extent and has clinical utility - 09/08/11
, Benjamin D. Horne, PhD, MPH a, c, Matthew J. Kolek, MD a, Joseph B. Muhlestein, MD, FACC a, b, Chrissa P. Mower, BS a, James J. Park, BS a, Heidi T. May, MSPH a, b, Nicola J. Camp, PhD c, John F. Carlquist, PhD a, bRésumé |
Background |
Variants at the 9p21 locus have been associated with coronary heart disease, but their precise disease phenotype and utility for clinical risk assessment are uncertain.
Methods |
Consenting patients with early-onset angiographic coronary artery disease (CAD) (n = 1,011) were compared with matched subjects (n = 545) free of angiographic disease and with a random population sample (n = 565). Cases and controls were genotyped for 4 variants, and ORs for angio-CAD were determined. Findings were validated in a separate set of cases and controls (n = 1,452).
Results |
Alleles were highly correlated (r2 ≥ 0.9), and all predicted angio-CAD compared with both control groups. Genotype at rs2383206 (minor allele frequency 45.9%), the most predictive (P < .0001), was associated with an adjusted odds ratio for angio-CAD of 1.39 (95% CI, 1.05–1.85) for heterozygote and 1.73 (1.26–2.37) for homozygote risk-allele carriers and explained 21% of population attributable risk and was independent of traditional risk factors and myocardial infarction. For the comparison of combined cases versus combined control samples (N = 3,573), CAD was predicted by high-risk allele homozygosity at P = 9 × 10−8. Despite this, extent of disease was not increased. Applied to patients with intermediate Framingham risk scores, 9p21 genotyping modified risk classification in 24%.
Conclusions |
Variants at the 9p21 locus robustly predict angiographic CAD prevalence, independent of standard risk factors, but not CAD extent or myocardial infarction; provide pathophysiological insights; and may be clinically useful in refining coronary heart disease risk classification.
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| The study was funded by grants from the National Institutes of Health, National Heart, Lung, and Blood Institute (R01HL071878) (both in Bethesda, MD), and the Deseret Foundation, Intermountain Healthcare, Salt Lake City, UT. |
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| This content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute or the National Institutes of Health. |
Vol 156 - N° 6
P. 1155 - décembre 2008 Retour au numéro
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