Published online before print April 21, 2009, doi: 10.1161/CIRCGENETICS.108.817338
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Original Articles |
Impact of Adding a Single Allele in the 9p21 Locus to Traditional Risk Factors on Reclassification of Coronary Heart Disease Risk and Implications for Lipid-Modifying Therapy in the Atherosclerosis Risk in Communities Study
From the Department of Molecular and Human Genetics (A.B.), Baylor College of Medicine, Houston, Tex; Center for Cardiovascular Disease Prevention and Section of Atherosclerosis and Vascular Medicine (C.M.B., V.N.), Methodist DeBakey Heart and Vascular Center and Baylor College of Medicine, Houston, Tex; Human Genetics Center and Institute of Molecular Medicine (K.L., E.B.), University of Texas-Houston Health Science Center, Houston, Tex; Department of Biostatistics (L.C.), University of North Carolina, Chapel Hill, NC; Division of Epidemiology and Community Health (A.R.F.), University of Minnesota School of Public Health, Minneapolis, Minn; and Texas Heart Institute and the University of Texas-Houston Health Science Center (J.T.W.), Houston, Tex.
Correspondence to Christie Ballantyne, MD, Center for Cardiovascular Disease Prevention and Section of Atherosclerosis and Vascular Medicine, Methodist DeBakey Heart and Vascular Center and Baylor College of Medicine, 6565 Fannin, MS A656, Houston, TX 77030. E-mail cmb{at}bcm.tmc.edu
Received August 27, 2008; accepted April 20, 2009.
Background— A single-nucleotide polymorphism on chromosome 9p21, rs10757274 (9p21 allele), has been shown to predict coronary heart disease (CHD) in whites. We evaluated whether adding the 9p21 allele to traditional risk factors (RFs) improved CHD risk prediction in whites from the Atherosclerosis Risk in Communities study and whether changes in risk prediction would modify lipid therapy recommendations.
Methods and Results— Whites (n=9998) in the Atherosclerosis Risk in Communities study for whom the 9p21 genotype and traditional RF information was available were included. Using Cox proportional hazards models, the Atherosclerosis Risk in Communities Cardiovascular Risk Score, which is based on traditional RFs, was determined. A total of 1349 individuals (13.5%) developed incident CHD events during a period of 14.6 years. Adding the 9p21 allele to traditional RFs was associated with a hazard ratio of incident CHD of 1.2 per allele (P<0.000003) and a significant increase in the area under the curve of the receiver operating characteristic from 0.782 to 0.786 (95% CI, 0.001, 0.007). The 9p21 allele’s greatest influence to the Atherosclerosis Risk in Communities Cardiovascular Risk Score was observed in the intermediate-low (>5% to 
10% 10-year CHD risk) and intermediate-high (>10% to 20% 10-year CHD risk) categories, with 12.1% and 12.6% reclassified, respectively. This may impact therapy because 90% of these reclassified individuals had low-density lipoprotein cholesterol >100 mg/dL.
Conclusion— Adding the 9p21 allele to traditional RFs in whites in the Atherosclerosis Risk in Communities study modestly improved CHD risk prediction in the intermediate categories.
Key Words: genetics • heart disease • risk factors • lipids
CLINICAL PERSPECTIVE
The online-only Data Supplement is available at http://circgenetics.ahajournals.org/cgi/content/full/CIRCGENETICS.108.817338/DC1.