The -174GG interleukin-6 genotype is protective from retinopathy and nephropathy in juvenile onset type 1 diabetes mellitus

Abstract

The aim of our study was to determine an association between the -174G>C IL-6 polymorphism (rs1800795) and occurrence of retinopathy and nephropathy in type 1 diabetes mellitus (T1DM) patients. Two hundred ten children/adolescents with long-standing T1DM (16.5 +/- 3.8 y; with diabetes duration of 8.4 +/- 3.0 y) were enrolled into the study. A group of 170 healthy young (16.9 +/- 5.2 y) sex-matched volunteers was qualified as the control. The IL-6 polymorphism was genotyped with the PCR-RFLP method. Serum and urine IL-6 concentrations were measured by the ultra-sensitive ELISA tests. The -174GG genotype was under represented in the diabetic patients compared with the controls. Patients with this genotype were free from nephropathy and retinopathy. The group of -174GG carriers was characterized by the highest urine IL-6 concentrations in relation to other genotypes. In the multivariate logistic regression analysis adjusted for age, duration of the disease, age of disease onset, HbA1c, and albumin excretion rate, the -174GG genotype was the only independent variable that significantly decreased the risk of jointly analyzed retinopathy and nephropathy [OR = 0.65; 95% CI = 0.52-0.82; p = 0.0003]. We propose that the -174GG patients are protected from late diabetic complications by different IL-6 dependent mechanisms.