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

Bárbara Angel; Lydia Lera; Hugo Sánchez; Amaya Oyarzún; Cecilia Albala

doi:10.1016/j.mgene.2015.10.003

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

Meta Gene. 2015 Oct 27:7:1-6. doi: 10.1016/j.mgene.2015.10.003. eCollection 2016 Feb.

Authors

Bárbara Angel¹, Lydia Lera¹, Hugo Sánchez¹, Amaya Oyarzún², Cecilia Albala¹

Affiliations

¹ Public Nutrition Unit, Institute of Nutrition and Food Technology (INTA), University of Chile, Chile.
² Human Nutrition Unit, Institute of Nutrition and Food Technology (INTA), University of Chile, Chile.

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)₂D₃ 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)₂D₃(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)₂D₃.

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.

Keywords: FokI polymorphism of vitamin D receptor; Type 2 diabetes; Vitamin D.