Tumor necrosis factor alpha -238 and -308 polymorphisms do not associate with insulin resistance in hypertensive subjects

Abstract

It is well established that, as a group, patients with essential hypertension are characterized by insulin resistance. Previous studies have shown that a biallelic polymorphism in the tumor necrosis factor (TNF)alpha promoter position -308 and -238 might be involved in the insulin resistance state in diabetic and/or nondiabetic subjects. We determined these polymorphisms in 235 nondiabetic hypertensive subjects and 246 unrelated normotensive controls. Fasting plasma glucose, insulin, lipoprotein, leptin, and TNFalpha concentrations were measured, in addition to plasma glucose and insulin responses to a 75-g oral glucose tolerance test (OGTT). Insulin sensitivity was also determined by an insulin suppression test in 69 hypertensive and 76 normotensive individuals. The results showed no association of these genotypic distributions between hypertensive and normotensive individuals both at -308 (GG, GA, and AA were 80.9%, 17.9%, and 1.3% in hypertensives, 84.2%, 15.4%, and 0.4% in normotensives, chi(2) = 1.68, P =.432) and at -238 (GG, GA, and AA were 98.3%, 1.7%, and 0% in hypertensives, 96.7%, 3.3%, and 0% in normotensives, chi(2) = 1.19, P =.276) sites. These results did not change even after adjustment for values of age and body mass index (BMI). Anthropometric measurements, fasting plasma glucose, insulin, lipoprotein concentrations, glucose, and insulin responses to OGTT, TNFalpha, and leptin concentrations were similar between the genotype at the -308 site both in hypertensive and normotensive groups. Insulin sensitivity, either measured by an insulin suppression test or homeostasis model assessment (HOMA) index, did not differ between the genotype at the -308 site in subjects with hypertension or normotension. Fasting plasma TNFalpha (10.2 alpha 0.5 pg/mL v 10.1 +/- 0.5 pg/mL, P =.928) concentrations did not differ between hypertensive and normotensive subjects even after adjustment for body fat and BMI values. We conclude that TNFalpha promoter gene polymorphisms at position -238 and -308 do not play a major role in the pathogenesis of insulin resistance in Chinese subjects with or without hypertension.