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

It is well established that, as a group, patients with essential hypertensi on are characterized by insulin resistance. Previous studies have shown tha t a biallelic polymorphism in the tumor necrosis factor (TNF)a promoter pos ition -308 and -238 might be involved in the insulin resistance state in di abetic and/or nondiabetic subjects. We determined these polymorphisms in 23 5 nondiabetic hypertensive subjects and 246 unrelated normotensive controls . Fasting plasma glucose, insulin, lipoprotein, leptin, and TNF alpha conce ntrations were measured, in addition to plasma glucose and insulin response s to a 75-g oral glucose tolerance test (OGTT). Insulin sensitivity was als o determined by an insulin suppression test in 69 hypertensive and 76 normo tensive individuals. The results showed no association of these genotypic d istributions 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 normot ensives, chi (2) = 1.19, P=.276) sites. These results did not change even a fter adjustment for values of age and body mass index (BMI). Anthropometric measurements, fasting plasma glucose, insulin, lipoprotein concentrations, glucose, and insulin responses to OGTT, TNF alpha, and leptin concentratio ns 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 dif fer between the genotype at the -308 site in subjects with hypertension or normotension. Fasting plasma TNF alpha (10.2 +/-0.5 pg/mL v 10.1 +/-0.5 pg/ mL, P=.928) concentrations did not differ between hypertensive and normoten sive subjects even after adjustment for body fat and BMI values. We conclud e that TNFa promoter gene polymorphisms at position -238 and -308 do not pl ay a major role in the pathogenesis of insulin resistance in Chinese subjec ts with or without hypertension. Copyright (C) 2001 by W.B. Saunders Compan y.