Association of Fokl (rs2228570) and Taql (rs731236) Polymorphisms of Vitamin-D Receptor (VDR) gene with the Diabetic Septic Foot Predisposition

Abstract

Abstract Diabetic septic foot (DSF) is one of the chronic consequences of diabetes mellitus (DM) and might lead to high rate of extremity amputations. Vitamin D is a steroid hormone that regulates calcium and phosphoruslhomeostasis and the recent epidemiologic studies evidenced the relationships between low vitamin D levels and multiple disease states, by regulating the transcription of a number of difierent cellular genes implicated in a variety of diseases. The action of vitamin D is mediated through its binding to nuclear vitamin D receptor (VDR).In this study we aimed to investigate the association of VDR) Fokl (C/T) (rs2228570) at Exon 2 and Taql (C/T) (rs731236) gene polymorphisms with the susceptibility to the development DSF in diabetic Sudanese patients. A total of 179 subjects were recruited for this study, including 86 diabetic septic foot (DSF= cases) and 93 diabetic (=c0ntro1s). The detection of VDR Fokl and Taql polymorphisms was done by PCR-RFLP using Fokl and Taql restriction enzymes. Our results showed that family history of diabetes was reported in 64.1% of the DSF. No gender differences was observed between cases and controls (P=O.26). 59.7% of the cases develop the disease alter Syears of the onset of diabetes. 38.6% and

68.5% of the DSF have retinopathy and neuropathy respectively, with three folds increased risk (P=0.01, OR=2.79, P=0.001, OR=3.3, respectively) compared to diabetics. No physical activity was reported in 74.3% of the DSF patients with significant difference between cases and controls (P=0.002). 54.9% and 32.9% of the DSF are smokers and alcohol consumers, respectively. Although the mutant genotypes (CT and TT) of Fok I polymorphism was observed in one third (31.4%) of the DSF, however no significant difference between cases and controls was reported (P =0.3l). Equal frequency (81.4%) of the mutant genotype (CT and TT) of T aql VDR polymorphism was reported in both DSF (cases) and DM (controls). These data suggest that the Fok] and Taql polymorphisms of the VDR gene are unlikely to contribute to DSF predisposition and other complications such as retinopathy and neuropathy might be implicated in the development of DSF. KEYWORDS: Diabetic septic foot, VDR polymorphisms, rs222857O (Fok!) and rs731236 (Taql)