Vitamin D receptor FokI polymorphism as a risk factor for painful diabetic neuropathy in type 2 diabetes mellitus patients

Painful diabetic neuropathy (PDN) is a common complication in patients with type 2 diabetes mellitus (T2DM) with disruption of vitamin D (VD) activity as one of the risk factors. Active VD exerts its biological functions through the vitamin D receptor (VDR), which polymorphisms in the VDR gene can impair. This study aims to establish VDR FokI and ApaI polymorphisms as risk factors for PDN. This case-control study used samples from T2DM patients with and without PDN. Neuropathic pain was diagnosed using the DN4 questionnaire, while FokI and ApaI polymorphisms were examined using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism method. Other factors examined included gender, hypertension, current insulin use, obesity, HbA1c levels, and dyslipidemia. A total of 64 subjects were involved in the study. The FokI polymorphism (CT+TT genotype) was a significant risk factor for PDN (OR 4.20; 95% CI [1.47-11.94]; p = 0.012). The T allele in the FokI polymorphism significantly increased the risk of PDN by 2.8 times (OR 2.78; 95% CI [1.28-6.01], p = 0.014). The ApaI polymorphism was not significantly associated with PDN. Diabetes duration ≥4.5 years and uncontrolled diabetes were other significant risk factors for PDN. Multivariate analysis identified three significant variables: FokI polymorphism (OR 5.00; 95% CI [1.37-18.24], p = 0.015), insulin use (OR 4.95; 95% CI [1.37-17.87], p = 0.015), and uncontrolled diabetes (OR 3.47; 95% CI [1.03-11.69], p = 0.045). The VDR FokI polymorphism with the T allele is a significant genetic risk factor for PDN in T2DM patients. The VDR ApaI polymorphism was not a significant risk factor for PDN.