Association of vitamin D and vitamin D receptor gene polymorphisms with chronic inflammation, insulin resistance and metabolic syndrome components in type 2 diabetic Egyptian patients

Abstract

BackgroundTo date the published data concerning the possible interplay between vitamin D (VitD) and Vit D receptor (VDR) gene polymorphism with the immune/inflammatory mediators in type 2 diabetes mellitus (DM) is insufficient. Some of the immune non-classical actions of vitamin D may point to its role in the pathogenesis of type 2 DM through down-regulation of cytokines (IL-6). Although there is evidence to support a relationship among vitamin D status, chronic inflammation and insulin resistance, the underlying mechanism requires further exploration. We aimed to investigate the role of vitamin D in chronic inflammation and insulin resistance in type 2 DM. Moreover, to examine the association of VDR gene polymorphisms [VDR 2228570 C > T (FokI); VDR 1544410 A > G (BsmI)] with the components of metabolic syndrome (MetSyn) in type 2 diabetic Egyptian patients .Subjects and methodsA total of 190 subjects were enrolled in this study, 60 controls and 130 type 2 diabetic patients (Group II). Group II was subdivided into 63 patients without MetSyn (subgroup IIa) and 67 patients with MetSyn (subgroup IIb). Genetic analysis for VDR gene polymorphisms was done in all subjects. VitD and IL-6 plasma levels were estimated.ResultsThe TT genotype for the VDR FokI was significantly more frequent in subgroup IIb than in subgroup IIa and controls (X2 = 6.83, P = 0.03 and X2 = 16.592, P = 0.000) respectively. The T allele was more frequent in the MetSyn group as compared to diabetics without MetSyn (p = 0.001), odds ratio (OR) and 95% CI for the T allele of C > T (FokI) = 2.30 (1.37–3.86). We did not detect any significant difference in VDR BsmI genotypes between patients and control groups (P = 0.947). FokI VDR was significantly associated with the lipid profile parameters, VitD and IL-6 plasma levels in subgroup IIa and associated with HOMA-IR, insulin, VitD, IL-6 levels, waist circumference (WC) and body mass index (BMI) in subgroup IIb while BsmI VDR variant was associated only with VitD values in both subgroups.ConclusionThe present study suggests an interaction between VDR polymorphisms and important components of MetSyn, VitD and pro-inflammatory cytokines (IL-6). FokI VDR polymorphisms may be linked to mild inflammation and insulin resistance and might represent a genetic determinant for developing MetSyn in type 2 diabetic Egyptian patients. The challenge is determining the mechanisms of VitD action for recommendation of VitD supplementation that reduces the risks of MetSyn, insulin resistance and progression to type 2 diabetes.

Associations between TaqI Polymorphisms in Vitamin D Receptor Gene and Type 2 Diabetes Mellitus in Obese Iraqi Population

“…In addition‚ the results seem to reinforce the association of the TT genotype with the susceptibility to the T2DM. On the other hand the result present study did not agree well with an observation that corroborated with a metaanalysis study [13]‚ in which the TT genotype association and the TaqI genotypes and allele non association with T2DM was clearly obtained. Results of this work is inconsistent with Errouagul [14] who observed that the tt allele was associated with T2DM in Morocco population.…”

Vitamin D Status and its Receptor Genes BsmI, FokI, ApaI, TaqI Polymorphism in Relation to Glucose Metabolism in Obese Iraqi Type 2 Diabetes Mellitus Patients

“…In addition, the results seem to reinforce the association of the FF genotype with the susceptibility to the T2DM. On the other hand, the present study did not find any significant differences in VDR gene polymorphism at position BsmI and ApaI between the T2DM patients and the controls‚ an observation that corroborated with a metaanalysis study by Mackawy and Badawi [32] in which the FF genotype association and the BsmI genotypes and allele non-association with T2DM was clearly obtained. Results of this work are inconsistent with Errouagulet [33] who observed that the ff allele was associated with T2DM in Morocco population.…”

Lack of association between FokI polymorphism in vitamin D receptor gene (VDR) & type 2 diabetes mellitus in the Tunisian population

“…Malecki et al 15 reported no significant difference in the distribution of the allele and genotype frequencies of the FokI polymorphism between 308 T2DM patients and 239 healthy controls from Poland similar to our study. However, in an Egyptian study, involving 63 patients with T2DM and 60 controls, the FokI variant was significantly associated with risk of T2DM only in patients with metabolic syndrome28. A meta-analysis of 10 studies involving 1562 cases and 1461 controls, showed that the FokI polymorphism was associated with an increased risk of T2DM (T vs. C: OR = 1.30, 95% CI = 1.17 - 1.45, P <0.001), especially in East Asians14.…”