Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Dec 13;58(25):2675-82.
doi: 10.1016/j.jacc.2011.08.054.

Genetic susceptibility to coronary heart disease in type 2 diabetes: 3 independent studies

Lu Qi  1 , Layla Parast, Tianxi Cai, Christine Powers, Ernest V Gervino, Thomas H Hauser, Frank B Hu, Alessandro Doria
Affiliations

Genetic susceptibility to coronary heart disease in type 2 diabetes: 3 independent studies

Lu Qi et al. J Am Coll Cardiol. .

Abstract

Objectives: The aim of this study was to evaluate whether coronary heart disease (CHD)-susceptibility loci identified by genome-wide association studies of the general population also contribute to CHD in type 2 diabetes.

Background: No study has examined the effects of these genetic variants on CHD in diabetic patients.

Methods: We genotyped 15 genetic markers of 12 loci in 3 studies of diabetic patients: the prospective Nurses' Health Study (309 CHD cases, and 544 control subjects) and Health Professional Follow-up Study (345 CHD cases, and 451 control subjects) and the cross-sectional Joslin Heart Study (422 CHD cases, and 435 control subjects).

Results: Five single-nucleotide polymorphisms, rs4977574 (CDKN2A/2B), rs12526453 (PHACTR1), rs646776 (CELSR2-PSRC1-SORT1), rs2259816 (HNF1A), and rs11206510 (PCSK9) showed directionally consistent associations with CHD in the 3 studies, with combined odds ratios (ORs) ranging from 1.17 to 1.25 (p = 0.03 to 0.0002). None of the other single-nucleotide polymorphisms reached significance in individual or combined analyses. A genetic risk score (GRS) was created by combining the risk alleles of the 5 significantly associated loci. The OR of CHD/GRS unit was 1.19 (95% confidence interval: 1.13 to 1.26; p < 0.0001). Individuals with GRS ≥8 (19% of diabetic subjects) had almost a 2-fold increase in CHD risk (OR: 1.94, 95% confidence interval: 1.60 to 2.35) as compared with individuals with GRS ≤5 (30% of diabetic subjects). Prediction of CHD was significantly improved (p < 0.001) when the GRS was added to a model including clinical predictors in the combined samples.

Conclusions: Our results illustrate the consistency and differences in the determinants of genetic susceptibility to CHD in diabetic patients and the general populations.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Receiver-Operating-Characteristic (ROC) Curves for CHD in Patients with Type 2 Diabetes
The curves are based on logistic regression models incorporating conventional risk factors age, BMI, smoking, glycemic control, history of hypertension, history of cholesterol, and HDL cholesterol, with and without the GRS.
See this image and copyright information in PMC

References

    1. Hunink MG, Goldman L, Tosteson AN, et al. The recent decline in mortality from coronary heart disease, 1980–1990. The effect of secular trends in risk factors and treatment. Jama. 1997;277:535–542. - PubMed
    1. Beckman JA, Creager MA, Libby P. Diabetes and atherosclerosis: epidemiology, pathophysiology, and management. Jama. 2002;287:2570–2581. - PubMed
    1. Zimmet P, Alberti KG, Shaw J. Global and societal implications of the diabetes epidemic. Nature. 2001;414:782–787. - PubMed
    1. Lusis AJ, Mar R, Pajukanta P. Genetics of atherosclerosis. Annu Rev Genomics Hum Genet. 2004;5:189–218. - PubMed
    1. Helgadottir A, Thorleifsson G, Manolescu A, et al. A common variant on chromosome 9p21 affects the risk of myocardial infarction. Science. 2007;316:1491–1493. - PubMed

Publication types