The G⁸⁹⁴-T⁸⁹⁴ exon 7 polymorphism in the endothelial nitric oxide synthase gene and blood pressure in a cohort of lead-exposed workers from Korea

Abstract

Research question. Is the G-T polymorphism in exon 7 of the endothelial nitric oxide synthase (eNOS) gene associated with increased blood pressure or increased susceptibility to the effects of lead on blood pressure in a cohort of lead-exposed workers from Korea? Background. Hypertension effects 24% of adult Americans, and increases risk of adverse cardiovascular outcomes. Several modifiable risk factors for hypertension have been identified, including overweight, poor diet, and physical inactivity. Some studies suggest that lead-exposure may be a modifiable risk factor for hypertension. Recently, interest has focused on genetic polymorphisms as susceptibility factors for hypertension. As nitric oxide (NO) is a central mediator of blood pressure homeostasis, polymorphisms in the gene for endothelial nitric oxide synthase (eNOS) have been theorized to be susceptibility factors for hypertension. Some---but not all---studies have found that the T-allele (the minor allele) of a G-T nucleotide substitution polymorphism in exon 7 of the eNOS gene is associated with increased risk of hypertension. This finding is support by reports suggesting that NO production may be decreased in individuals with the T-variant allele. Methods. 793 lead-exposed workers were genotyped for the polymorphism using a PCR-based assay. Regression was used to model the genotype-blood pressure association and genotype as an effect-modifier of the lead-blood pressure association. Age, gender, BMI, education, smoking, and alcohol consumption were included in the model. Results. 84.9% of individuals were homozygous GG, 14.4% were heterozygous GT, and 0.8% were homozygous TT. The T-allele was not significantly associated with systolic or diastolic blood pressure. After adjustment for potential confounders, individuals with the T-allele had 0.7 +/- 1.5 mm Hg lower systolic blood pressure and 0.1 +/- 1.0 mm Hg than those without the allele [+/-SE]. After adjustment for potential confounders, a 10-percentile increase in tibia lead was associated with a 0.08 +/- 0.45 mm Hg increase in systolic blood pressure in those with the T-allele, and a 0.62 +/- 0.21 mm Hg increase in systolic blood pressure in those without the allele (interaction effect not significant). Conclusions: These data provide no evidence for increased blood pressure or increased sensitivity to the effects of lead on blood pressure in individuals with the T-allele.