The tumour necrosis factor alpha-238 G→A and-308 G→A promoter polymorphisms are not associated with insulin sensitivity and insulin secretion in young healthy relatives of Type II diabetic patients

Aims/hypothesis. Tumour necrosis factor-alpha (TNF-alpha) is believed to influence skeletal muscle insulin resistance. Two G --> A transitions in the promoter region of TNF-alpha at position -238 and -308 have been identified that could play a part in transcriptional regulation of the gene. Insulin resistance is an independent familial trait that predicts the development of Type II (non-insulin-dependent) diabetes mellitus. We investigated the influence on insulin sensitivity and insulin secretion of both polymorphisms in a cohort of young healthy relatives of patients with Type II diabetes. Methods. We examined 109 first-degree relatives of Caucasian patients with a history of Type II diabetes, wine underwent extensive metabolical and anthropometrical. phenotyping, and determined the TNF-alpha -238 and -308 G --> A promoter polymorphisms. Results. For the -238 polymorphism, 83 probands (76.1%) were homozygous for the G-allele, 25 probands (22.9%) were heterozygous and 1 proband (0.9%) was homozygous for the A-allele. For the -308 polymorphism, 83 probands (76.1%) were homozygous for the G-allele, 24 probands (22.0%) were heterozygous and 2 probands (1.18%) were homozygous for the A-allele. Probands with and without the polymorphism did not differ in insulin sensitivity (p = 0.78), insulin-concentrations and C-peptide concentrations in oral glucose tolerance tests (p > 0.05). Conclusions/interpretation. We could not detect an association between insulin sensitivity or insulin secretion and TNF-alpha promoter polymorphisms in our cohort. The polymorphisms occur at the Same frequencies in probands with either low or high insulin sensitivity.