The G-T Polymorphism in the Gene for Endothelial Nitric Oxide Synthase and Blood Pressure in Lead-Exposed Workers From Korea

We evaluated whether the G -T 894 polymorphism in exon 7 of the endothelial nitric oxide synthase (eNOS) gene is associated with blood pressure or modifies the relation between lead dose and blood pressure in 803 lead workers in Korea. A total of 84.9% of individuals were homozygous GG, 14.4% heterozygous GT, and 0.8% homozygous TT. The T 894 allele was not significantly associated with systolic or diastolic blood pressure. The prevalence of hypertension did not differ by T 894 status (OR 0.82; 95% CI 0.50–1.37). There was no evidence of effect modification by eNOS genotype on relations of lead dose with blood pressure. These data provide no evidence that the T 894 allele is associated with higher blood pressure or modifies the association of lead dose with blood pressure. (J Occup Environ Med. 2004;46:584–590) L ead exposure has been associated with increased blood pressure in some, but not all, studies in humans. Overall, the body of epidemiologic literature would support the inference that lead causes elevations in blood pressure, even at relatively low levels. In addition to the epidemiologic evidence, there is evidence from animal models, because animals fed lead have elevations in blood pressure. Some evidence suggests that lead could increase blood pressure by lowering steadystate levels of nitric oxide (NO), a principal endothelium-derived relaxing factor and one of the body’s key modulators of vascular resistance. Constitutively produced in the endothelium by endothelial nitric oxide synthase (eNOS), NO diffuses into the vascular wall to relax the vascular smooth muscle. Animal and human studies unequivocally demonstrate that reduced steady-state NO levels substantially increase blood pressure. Lead could increase blood pressure either through decreasing production of NO and/or increasing NO inactivation. Polymorphisms in the gene for eNOS have been suggested to be susceptibility factors for hypertension, with a G-T nucleotide substitution polymorphism in exon 7 receiving much recent attention. The T allele, the minor allele, is prevalent at 10% to 40% (depending on the population sampled); studies in From the Department of Epidemiology and Preventive Medicine, University of Maryland Baltimore, Baltimore, Maryland (Dr Lustberg); the Departments of Environmental Health Sciences (Drs Schwartz and Silbergeld) and Epidemiology (Dr Schwartz), Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; the Department of Medicine (Dr Schwartz), Johns Hopkins School of Medicine, Baltimore, Maryland; the Institute of Industrial Medicine, Soonchunhyang University, Chonan, Korea (Dr Lee); and the Department of Community and Preventive Medicine, The Mount Sinai School of Medicine, New York, NY (Dr Todd). Address correspondence to: Brian S. Schwartz, MD, MS, Division of Occupational and Environmental Health, Johns Hopkins Bloomberg School of Public Health, Room W7041, 615 North Wolfe Street, Baltimore, MD 21205; E-mail: [email protected]. Copyright © by American College of Occupational and Environmental Medicine