Abstract
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.