Objectives: Tumor necrosis factor alpha (TNFalpha) is expressed primarily in adipocytes and elevated levels of this cytokine have been linked to obesity and insulin resistance. Several studies have shown statistical evidence of linkage between obesity and the chromosomal region encompassing the TNFalpha gene, suggesting that TNF alpha and/or a nearby gene is involved in the pathogenesis of obesity. Recently we analyzed the -308 TNFalpha polymorphism and that of HSP70-2 gene in Tunisian patients with obesity and no significant difference in allele frequencies of the -308 TNFalpha polymorphism was found between obese patients and controls. In contrast, polymorphism in HSP70-2 gene was found to be highly associated with obesity. Both TNFalpha and HSP70-2 genes have been mapped within the major histocompatibility complex (MHC). We designated a case-controlled study to investigate a potential association of genetic variation of the TNFalpha and that of the heat shock protein 70-2 (HSP70-2) with type 2 diabetes.
Methods: We used the polymerase chain reaction and restriction enzyme to characterize the variation of the TNFalpha promoter region and that of the HSP70-2 gene in 280 unrelated Tunisian patients with type2 diabetes and 274 healthy control subjects.
Results: Analysis of the -308 TNFalpha polymorphism in patients with type 2 diabetes and in control subjects revealed that the heterozygous TNF1/TNF2 genotype was significantly less frequent in the patient group (p=0.003), suggesting that TNF1/TNF2 may be considered as a protective marker against type 2 diabetes (OR=0.58). In contrast, a significant relative risk of type 2 diabetes was found associated with the P2-HSP70-2 homozygous genotype in non obese diabetic subjects (OR=1.97; p=0.0012).
Conclusion: These results along with those showing high frequency of P2-HSP70-2 genotype in obese Tunisians, suggest that HSP70-2 polymorphism has susceptibility implications in both obesity and diabetes.