Impaired endothelial function with decreased
nitric oxide production is shared by
insulin resistance and
essential hypertension. Although there are limited data on the association between the
endothelial nitric oxide synthase (eNOS) G894T polymorphism and
hypertension, information is absent on the combined effects of eNOS G894T genotype and
insulin resistance status on blood pressure (BP) levels and the familial risk of
hypertension. This aspect was examined in a community-based sample of 1021 unrelated African American and white young adults aged 19 to 38 years. African Americans displayed a lower frequency of the T894 allele than whites (0.105 v 0.324, P < .001). After adjusting for sex, age, and body mass index (BMI), noncarriers versus carriers of the T894 allele had significantly higher systolic (SBP), diastolic (DBP) BP and mean arterial pressure (MAP) levels (111.7 v 109.2 mm Hg for SBP; 73.6 v 72.3 mm Hg for DBP; 86.3 v 84.6 mm Hg for MAP), with both African Americans and whites showing similar trends. This association was modulated by
insulin resistance status, measured by the homeostasis model assessment of
insulin resistance (HOMA IR) using fasting
insulin and
glucose. Subjects with high
insulin resistance (above the median HOMA IR) showed significantly greater differences in BP levels between noncarriers and carriers of the T894 allele. Furthermore, the G894T genotype and
insulin resistance also showed a combined effect on the prevalence of parental
hypertension, a measure of familial risk, with noncarriers versus carriers in the high
insulin resistance group showing higher prevalence (70.5% v 51.3%, P = .006, adjusted for race). Thus, the allelic variation (G894T) in the eNOS gene locus in conjunction with
insulin resistance may be one factor contributing to the predisposition to
hypertension.