Osteoprotegerin gene rs2073617, rs2073618 and rs3134069 polymorphisms in patients with type 2 diabetes. Polymorphism rs2073618 - a new sex-specific genetic marker as a diabetic foot risk factor.

Abstract

INTRODUCTION Diabetic foot (DF) is severe diabetes (DM) complication leading to delayed wound healing and may result in amputation. Osteoprotegerin (OPG) is a protein taking part in pathogenesis of DF occurrence. OBJECTIVES The aim of the study was to evaluate the frequency of alleles in TNFRSF11B gene polymorphisms rs2073617, rs2073618 and rs3134069 in patients with DF, DM and healthy control group. PATIENTS AND METHODS We included 877 individuals: 122 with DF, 293 with type 2 DM and 462 healthy control group. RESULTS The study showed that rs2073618 allele C is a risk factor for DF occurrence comparing to control group in allele G carriers (OR=1.72;p=0.035;95%CI:1.03-2.86;OR-Odds Ratio; CI-Confidence Interval) and for males in homozygous (OR=3.16;p=0.011;95%CI:1.27-7.87), with allele G carriers (OR=3.28;p=0.002;95%CI:1.48-7.24) and heterozygous (OR=3.33;p=0.002;95%CI:1.47-7.540) comparisons. Similar association is observed between DF and DM groups in allele G carriers (OR=2.56;p=0.020;95%CI:1.13-5.77), homozygous (OR=2.30;p=0.076;95%CI:0.91-5.85) and heterozygous male limited (OR=2.69;p=0.018;95%CI:1.16-6.22) comparisons. Comparing to control group, association is present for neuropathic DF in heterozygous (OR=2.5;p=0.044;95%CI:1.00-6.23), allelic male limited (OR=3.17;p=0.029;95%CI:1.07-9.38) and heterozygous (OR=3.49;p=0.02;95%CI:1.15-10.58) comparisons. Rs2073617 allele A protected against DF in females (OR=0.45;p=0.045;95%CI:1.00-4.92, comparison vs. controls) in a heterozygous comparison. Rs3134069 did not appear to be DF risk factor. CONCLUSIONS There is a possibility to use genotyping for risk assessment of DF and neuropathic DF occurrence in people with DM.