FokI polymorphism in vitamin D receptor gene: Differential expression of TNFα in peripheral mononuclear cells of type 2 diabetic subjects

INTRODUCTION: FokI polymorphism has been associated with obesity and type 2 diabetes (T2D) in some populations. OBJECTIVE: To investigate the frequencies of a genetic polymorphism of Vitamin D receptor (FokI) in patients with T2D and control subjects and investigate the role of 1,25(OH)(2)D(3) in the expression of pro-inflammatory markers in peripheral blood mononuclear cells (PBMCs). METHODS: The case–control study was conducted in 160 patients with T2D and 160 control subjects, men and women (30–74 years old). The genotype and allele frequency of FokI polymorphisms were determined in these subjects. Subsequently a subgroup of 40 subjects was included from which PBMCs were removed. In vitro, the culture medium was supplemented with two different concentrations of 1,25(OH)(2)D(3)(10(− 8) M and 10(− 10) M). The expression profiles of TNFα and mRNA were analysed by qPCR, and GAPDH and β-actin were used as housekeeping genes. RESULTS: The control subjects have an increased frequency of the FF genotype. In subjects with T2D, the ff genotype was associated with higher HOMA-IR values than individuals with genotype Ff (p = 0.021). In vitro study in PBMCs showed differential expression of TNFα mRNA by FokI genotype, with a lower expression of this marker of inflammation in FF genotype subjects at a concentration of 10(− 8) M of 1,25(OH)(2)D(3). CONCLUSION: Our data suggest that VDR FokI polymorphism is associated with T2D, and the genotypes Ff and ff of this variant show a reduced response or resistance to the anti-inflammatory action of VitD, which could indicate a functional role of FokI polymorphism of VDR.