Association Aanalysis Of Vitamin D Receptor Gene Polymorphism And Serum Vitamin D Levels In Subjects With Impaired Glucose Tolerance

ObjectivesTo investigate the distribution of the FokI polymorphism in vitamin D receptor (VDR)gene in the Han nationality population of Taian city to further assess the association ofVDR FokI polymorphism and the levels of serum25-OH-VD3with insulin resistance insubjects with impaired glucose tolerance (IGT). By doing so, we try to explore thepathogenesis of IGT from the perspective of molecular biology so as to add some theorieson guiding how to prevent the progress of IGT to type2diabetes in the level of theory.Subjects and methodsThe study design was case-control.94subjects with IGT (according to the criteria ofWorld Health Organization issued in1999) and54healthy physical examinees wereenrolled as the control group. Blood of two groups were collected and DNA was extractedrespectively by DNA Extraction Kit. Vitamin D receptor gene FokI polymorphism wasevaluated by polymerase chain reaction-restriction fragment length polymorphism in allsubjects. Genotype and allele frequencies of all subjects were calculated. Levels of totalcholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), lowdensity lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG) and fasting insulin(FINS) were examined. Insulin resistance index (HOMA-IR) was calculated from FPG andFlns. ELISA was used for the detection of serum25-dihydroxy vitamin D3levels. Theassociation of serum25-OH-VD3levels and vitamin D receptor gene FokI polymorphismwith insulin resistance in IGT subjects were analysized by SPSS13.0software.Results1.Level of serum25-OH-VD3lower than30ng/ml accounted for63.8%of all cases.Comparison of clinical parameter between two groups was as follow: compared withcontrols, subjects with IGT had a significantly higher level of BMI（26.07±2.50vs22.82±1.59kg/m2）、FINS (16.32±7.29vs8.11±4.06uIu/ml）、HOMA-IR（4.14±1.88vs 2.04±1.07)、TG（1.93±0.18vs1.47±0.21）、TC（5.46±0.72vs5.25±0.31）and LDL-C（3.14±0.94vs2.84±0.24） but a markedly lower level of serum25-OH-VD3(22.05±2.37vs32.04±2.64, P<0.05）.There was a significant negative correlation between serum25（OH）VD3level and HOMA-IR（r=-0.813）、BMI（r=-0.324）and waist circumference（r=-0.440）.2. VDR gene FokI polymorphism was detected in the IGT group and the healthy con-trol group. Its distribution conformed to Harding-Winberg equilibrium. By usingPCR-RFLP technique to detect the VDR gene FokI polymorphism in Han populatio-n ofTaian and surrounding areas, the there genotypes FF, Ff, ff were detected in the VDR FokIsites. A significant difference was observed between IGT and control group for thecomparison of allele and genotype frequencies (f:46.8%versus25.9%; FF:30.9%versus57.4%; Ff:46.9%versus33.3%; ff:22.3%versus9.3%). Subjects carrying f allele had a2.465fold increased risk for IGT compared with those carrying F allele. The comparisonof f/f versus F/f and f/f versus F/F showed a diffrential IGT susceptibility (OR=2.613,95%CI=1.239-5.512,P=0.018; OR=4.49，95%CI=1.496-13.473,P=0.01). HOMA-IR of thegroup with FF genotype was significantly lower than that of the groups with Ff or ffgenotype (2.46±0.37versus3.91±0.46or7.05±2.37).Conclusions1.Vitamin D deficiency is common in the population.2. Serum25-OH-VD3levels and insulin resistance were negatively correlated.3. FokI polymorphism of the VDR gene exists in the Han population in Tai’an andsurrounding areas. Allele “f” may be a susceptible gene contributing to the development ofIGT. f allele was associated with insulin resistance.Serum25-OH-VD3and vitamin Dreceptor gene FokI polymorphism may play a role in insulin resistance in the Impairedglucose tolerance population. Subjects carrying the f allele were more susceptible toinsulin resist-ance.