Author + information
- Kenneth Chan, MPharm,
- Anna Motterle, MSc,
- Ross C. Laxton, BSc and
- Shu Ye, MD, PhD⁎ ()
- ↵⁎Barts and the London School of Medicine, Queen Mary University of London, John Vane Science Building, Charterhouse Square, London EC1M 6BQ, United Kingdom
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).
Thus, the results of our study support that there is an association between 9p21 and CAD severity, arguing for the notion that the 9p21 variant predisposes to initiation as well as progression of CAD (2). In addition, our data highlight the need for further detailed studies to assess the effects of 9p21 on CAD phenotypes and its potential interactions with other cardiovascular risk factors such as diabetes mellitus.
Please note: The authors are grateful for the support of the British Heart Foundation. This work forms part of the research themes contributing to the translational research portfolio of Barts and the London Cardiovascular Biomedical Research Unit, which is supported and funded by the National Institute of Health Research.
- American College of Cardiology Foundation
- Dandona S.,
- Stewart A.F.,
- Chen L.,
- et al.
- Anderson J.L.,
- Horne B.D.