Common Variants of the Endothelial Nitric Oxide Synthase Gene and the Risk of Coronary Heart Disease Among U.S. Diabetic Men
- 1Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts
- 2Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
- 3Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
- 4Department of Laboratory Medicine, Children’s Hospital and Harvard Medical School, Boston, Massachusetts
- Address correspondence and reprint requests to Cuilin Zhang MD, PhD, Department of Nutrition, Harvard School of Public Health, 665 Huntington Ave., Boston, MA 02115. E-mail: nhcui{at}channing.harvard.edu or nhbfh{at}channing.harvard.edu
Abstract
Endothelial nitric oxide synthase (eNOS) gene represents a promising candidate gene for coronary heart disease (CHD) because of its impact on eNOS activity. We systematically examined the associations of eight variants of the eNOS gene (two potentially functional variants [−786T>C and Glu298Asp] and six tagging single nucleotide polymorphisms) with CHD risk in a large cohort of diabetic patients. Among 861 diabetic men (>97% Caucasian) from the Health Professionals Follow-Up Study, 220 developed CHD, and 641 men without cardiovascular disease were used as control subjects. Genotype distributions of −786T>C and Glu298Asp polymorphisms were not significantly different between case and control subjects. CHD risk was significantly higher among men with the variant allele at the rs1541861 locus (intron 8 A/C) than men without it (adjusted odds ratio 1.5 [95% confidence interval 1.1–2.1]). Moreover, among control subjects, plasma soluble vascular cell adhesion molecule concentrations were significantly higher among carriers of this allele (P 0.019) and carriers of the variant allele of the −786T>C (P 0.010), or the Glu298Asp polymorphism (P 0.002), compared with noncarriers. In conclusion, our data suggested that −786T>C, Glu298Asp, and an intron 8 polymorphism of the eNOS gene are potentially involved in the atherogenic pathway among U.S. diabetic men.
- CABG, coronary artery bypass grafting
- CHD, coronary heart disease
- CRP, C-reactive protein
- eNOS, endothelial nitric oxide synthase
- ICAM, intercellular cell adhesion molecule
- NCBI, National Center for Biotechnology Information
- sICAM, soluble intercellular cell adhesion molecule
- SNP, single nucleotide polymorphism
- sVCAM, soluble vascular cell adhesion molecule
- VCAM, vascular cell adhesion molecule
Footnotes
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact
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- Accepted April 3, 2006.
- Received November 26, 2005.
- DIABETES
