Heart Care Info - Heart Disease Prevention & Treatment

Common Variant on Chromosome 9p21 Predicts Severity of Coronary Artery Disease

K Chan, A Motterle, RC Laxton... - Journal of the American ..., 2011 - Am Coll Cardio Found Although some diversity is evident in patterns of regional LV systolic dysynergy (ballooning), each of the variants is similar to the classic circumferential mid and apical LV dyskinesia with sparing of the basal segment. Subclassifying and renaming this ...

Kenneth Chan, M Pharm, Anna Motterle, M Sc, Ross C. Laxton, B Sc and Shu Ye, MD, Ph D*

We read with great interest the paper by Dandona et al. (1) and the accompanying editorial commentary by Anderson and Horne (2), published in a recent issue of the Journal. Dandona et al. (1) elegantly showed an association between a variant (SNP rs1333049) on chromosome 9p21 and coronary artery disease (CAD) severity represented by the number of coronary arteries with >50% stenosis in 2 cohorts of CAD patients who did not have diabetes mellitus (1). This provides novel evidence for an influence on the extent of coronary arterial lesions by the 9p21 variant, which was identified recently by genome-wide association studies to be a major genetic determinant that increases the risk of CAD.

Interestingly, several previous studies did not find the association between 9p21 and CAD severity defined by the number of coronary arteries with significant stenosis (3 5). In their report, Dandona et al. (1) speculated on several possible explanations, 1 of which is the inclusion of CAD patients with diabetes mellitus in the previously studies, which might confound and obscure the effect of 9p21 on CAD.

To investigate this possibility, we undertook analyses in a cohort of CAD patients (mean age 63 years, n = 1,094) recruited previously in the SAS (Southampton Atherosclerosis Study) (6). The subjects had >50% stenosis in at least 1 major epicardial coronary artery and were all of European ancestry. When CAD patients with diabetes mellitus (n = 146) were excluded, we observed an association between the risk allele (C allele) of the 9p21 SNP rs1333049 and increased risk of 3-vessel disease (3VD) defined by >50% stenosis in the 3 major coronary arteries (p = 0.022) (Fig. 1). Logistic regression analysis showed that each copy of the risk allele was associated with a 30% increased risk of 3VD (odds ratio: 1.30 [95% confidence interval: 1.04 to 1.63]) after adjusting for age, sex, smoking, hypertension, hypercholesterolemia, lipid-lowering treatment, and body mass index. However, when the CAD patients with diabetes mellitus were included in the analysis, the relationship between SNP rs1333049 and CAD severity became nonsignificant statistically (p = 0.077). This finding is in line with the possibility of an obscuring effect of diabetes mellitus, suggested by Dandona et al. (1).

Presented in the column chart are percentages of patients with 3-vessel disease (3VD) (n = 223) as a function of genotype. The p value was derived from logistic regression analysis with adjustment for age, sex, smoking, hypertension, hypercholesterolemia, lipid-lowering treatment, and body mass index. Patients with diabetes mellitus were excluded. CAD = coronary artery disease.