Association of tumor necrosis factor alpha, interferon gamma and interleukin 10 gene polymorphisms with peripheral neuropathy in South Indian patients with type 2 diabetes.

Unlabelled: Diabetic peripheral neuropathy (DPN) is a major global health threat and a common complication of diabetes. Peripheral nerve complications due to irregular cytokine production are eminent factors in many inflammatory diseases. The present study focused on gene polymorphisms of pro and anti-inflammatory cytokines that may be responsible for nerve damage in diabetic neuropathy. We examined three common functional SNPs primarily at the positions on genes of tumor necrosis alpha (TNFalpha) -308G/A, interferon gamma (IFNgamma) +874A/T and interleukin (IL) 10 -1082G/A in order to establish their association with peripheral neuropathy in type 2 diabetes.

Results: Genotypic frequencies obtained from TNFalpha -308G/A gene analysis in DPN group comprised 86.4% of G/A, 10.6% of G/G and 3% of A/A genotype, where as the control group had 94% of G/A, 2% of G/G and 4% of A/A which could not reach the statistical significance with the disease after Bonferroni correction. The IFNgamma +874 A/T polymorphism in patient group revealed 33.3% of A/A, 47.5% of A/T and 19.2% of T/T genotype. The A/A genotype had attained statistical significance of P=0.04 (P corrected); OR 2; 95% CI 1.14-3.64 when compared to controls. The IL10 -1082 G/A polymorphism in the patient group has showed 62.6% of A/A, 21.2% of G/A, 16.2% of G/G genotype, revealing significant association with G/G genotype (P<0.01, OR 2.9; 95% CI 1.47-5.84) when compared to controls.

Conclusion: Our findings indicate that the tested markers within the IFNgamma and IL-10 genes, but not the TNFalpha gene, are significantly associated with peripheral neuropathy in South Indian type 2 diabetic patients. The study shows that the 'high-producer' IL-10 -1082 G/G genotype and the 'low-producer' IFNgamma +874 A/A genotype may be responsible for the down regulation of immune response leading to inflammation in this setting.