Type 2 Diabetes And Vitamin D, Vitamin D Receptor Gene Polymorphisms

ObjectiveThe aim of the study was to explore the relationship among vitamin D, VDR gene polymorphisms and type 2 diabetes mellitus (T2DM), and the influence of gene-environment interaction on T2DM.MethodsA case-control study was conducted in Houzhai county, Zhengzhou city and Qiaomiao county of Jiaozuo city of Henan province from January to May 2013 according to the study design. Total 286 T2DM cases were recruited as T2DM group and 286 healthy subjects who were matched with T2DM group in age (±5 years old) and sex were recruited. All subjects were accepted questionnaire and physical examination, at the same time fasting blood samples were collected. The concentrations of serum total cholesterol, triglycerides, high-density lipoprotein cholesterol were determined by automatic biochemical analyzer. Serum 25(OH)D3 and 1,25(OH)2D3 levels were determined using enzyme linked immunosorbent assay (ELISA). The rs2189480 and rs3847987 of VDR gene polymorphisms were genotyped using TaqMan probes Real-Time PCR procedure. Haplotype was analyzed by Haplo. Stats package. Multifactor dimensionality reduction software (MDR) was used to evaluate the gene-environment interaction. Other statistical analysis was performed using the SPSS software, version 21.0. All statistical tests were 0.05 as a cutoff for significance.Results1. The relationship between VDR gene polymorphisms and T2DM.Individuals with rs2189480 CC genotype (OR=0.448,95% CI:0.256,0.786) and allele C (OR=0.753,95% CI:0.589,0.962) may be related to the decreased risk of T2DM. Individuals with rs3847987 allele A may be related to the increased risk of T2DM (OR-1.457,95% CI:1.085,1.957). Individuals with haplotype CC may be related to the decreased risk of T2DM (OR=0.729,95% CI:0.543,0.978).2. Vitamin D level in surum and T2DM.Sserum 25(OH)D3 levels were 32.33±33.18,38.87±41.00 ng/ml and the serum 1,25(OH)2D3 levels were 31.07±40.39,42.78±58.41pg/ml in cases and the controls repectively. Serum 25(OH)D3 and 1,25(OH)2D3 levels in cases were significantly lower than that in controls (P<0.05 respectively).Serum 25(OH)D3 levels and 1,25(OH)2D3 levels in T2DM cases with rs2189480 CA genotype and rs3847987 CC genotype were significantly lower than the control subjects after stratified by VDR genotypes (P<0.05 respectively). Serum 25 (OH) D3 levels in cases without family history of T2DM were significantly lower than those in control group (P<0.05 respectively) after stratified by family history of type 2 diabetes. Serum 1,25(OH)2D3 levels in T2DM group who were for mild physical activity, high levels of physical activity, and no family history of T2DM were significantly lower than those in control group (P<0.05 respectively).3. The relationship between gene-environment interaction and T2DM.Interaction of rs2189480 polymorphism, rs3847987 polymorphism in VDR gene and physical activity may be related to the increased risk of T2DM (OR=2.53, 95% CI:1.81,3.54).Conclusion1. VDR gene rs2189480 and rs3847987 polymorphisms were associated with the risk of T2DM. Haplotype CC (rs2189480, rs3847987) was associated with the decreased risk of T2DM.2. Serum 25(OH)D3 levels and 1,25(OH)2D3 levels in T2DM patients were significantly lower that in control group.3. Interaction of rs2189480 polymorphism, rs3847987 polymorphism in VDR gene and physical activity may be related to the increased risk of T2DM.