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-α (TNF-α) is believed to influence skeletal muscle insulin resistance. Two G → A transitions in the promoter region of TNF-α 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, who underwent extensive metabolical and anthropometrical phenotyping, and determined the TNF-α–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-α promoter polymorphisms in our cohort. The polymorphisms occur at the same frequencies in probands with either low or high insulin sensitivity. [Diabetologia (2000) 43: 181–184] [ABSTRACT FROM AUTHOR]