Background: To 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 methods: A 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.
Results: The TT genotype for the VDR FokI was significantly more frequent in subgroup IIb than in subgroup IIa and controls (X (2) = 6.83, P = 0.03 and X (2) = 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.
Conclusion: The 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.
Keywords: BMI, body mass index; CI, confidence intervals; CRP, C-reactive protein; DBP, diastolic blood pressure; DM, diabetes mellitus; FBG, fasting blood glucose; FPI, fasting plasma insulin; HDL-C, high density lipoprotein cholesterol; HOMA, Homeostasis of Metabolic Assessment; HPLC, High performance liquid chromatography; HbA1c, glycated hemoglobin; IL-6, interleukin -6; IRS, insulin receptor substrates; Insulin resistance; Interleukin-6 (IL-6); LDL-C, low density lipoprotein cholesterol; MetSyn, metabolic syndrome; Metabolic syndrome; NHANES III, National Health and Examination Survey; OR, odds ratio; PGs, pro-inflammatory prostaglandins; PTH, parathyroid hormone; Polymorphisms; Pro-inflammatory cytokines; SBP, systolic blood pressure; SD, standard deviation; SOCS, suppressors of cytokine signaling; TC, total cholesterol; TG, triglyceride; Type 2 diabetes mellitus (DM); VDR, Vit D receptor; VitD, Vitamin D; Vitamin D; Vitamin D Receptor gene; WC, waist circumference; X2, Chi-square.