Osteoprotegerin gene rs2073617 and rs3134069 polymorphisms in type 2 diabetes patients and sex‑specific rs2073618 polymorphism as a risk factor for diabetic foot

INTRODUCTION Diabetic foot is a severe diabetic complication, which may result in ulcerations that are unresponsive to treatment and in lower limb amputation. Osteoprotegerin is a protein that is involved in the pathogenesis of diabetic foot. OBJECTIVES The aim of the study was to evaluate the frequency of alleles in the TNFRSF11B gene rs2073617, rs2073618, and rs3134069 polymorphisms in patients with diabetic foot, diabetes, and healthy controls. PATIENTS AND METHODS The study comprised 877 patients, including 122 with diabetic foot, 293 with type 2 diabetes without diabetic foot, and 462 healthy controls. RESULTS In the rs2073618 polymorphism, the C allele was a risk factor for diabetic foot in patients with diabetes in the allelic variants [CC] vs. [CG + GG] (odds ratio [OR], 1.72; 95% confidence interval [CI], 1.03-2.86; P = 0.035), and in men in the following allelic variants: CC vs. GG (OR, 3.16; 95% CI, 1.27-7.87; P = 0.011), CC vs. CG (OR, 3.33; 95% CI, 1.47-7.54; P = 0.002), and [CC] vs. [CG + GG] (OR, 3.28; 95% CI, 1.48-7.24; P = 0.002). A similar association was observed between men with diabetic foot and those only with diabetes in the following allelic variants: CC vs. GG (OR, 2.30; 95% CI, 0.91-5.85; P = 0.076), CC vs. CG (OR, 2.69; 95% CI, 1.16-6.22; P = 0.018) and [CC] vs. [CG + GG] (OR, 2.56; 95% CI, 1.13-5.77; P = 0.02). For patients with neuropathic diabetic foot, the association was demonstrated in variant CC vs. CG (OR, 2.5; 95% CI, 1.00-6.23; P = 0.044) and only for men in the following allelic variants: [CC] vs. [CG + GG] (OR, 3.17; 95% CI, 1.07-9.38; P = 0.029) and CC vs. CG (OR, 3.49; 95% CI, 1.15-10.58; P = 0.02). The A allele of the rs2073617 polymorphism protected women in variant AA vs. AG against diabetic foot compared with controls (OR, 0.45; 95% CI, 1.00-4.92; P = 0.045). The rs3134069 polymorphism was not observed to be a risk factor for diabetic foot. CONCLUSIONS The analysis of the TNFRSF11B gene may be used to assess the risk of diabetic foot and neuropathic diabetic foot in patients with type 2 diabetes.