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Am Heart J. 2008 Dec;156(6):1155-1162.e2. doi: 10.1016/j.ahj.2008.07.006. Epub 2008 Oct 11.

Genetic variation at the 9p21 locus predicts angiographic coronary artery disease prevalence but not extent and has clinical utility.

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  • 1Cardiovascular Department, Intermountain Medical Center, Murray, UT 84107, USA. jeffrey.anderson@imail.org

Abstract

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 (r(2) > or = 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 x 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.

PMID:
19033013
[PubMed - indexed for MEDLINE]
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