The Correlation Of Vitamin D Receptor Gene Polymorphismswith Type 2 Diabetes And Dyslipidemias

ObjectiveTo explore the correlation of vitamin D receptor gene ApaⅠ and TaqⅠ polymorphisms with type 2 diabetes mellitus(T2DM) and dyslipidemias, analyze the risk factors of T2 DM and dyslipidemias.Methods A case-control study including 286 T2 DM patients(dyslipidemias 164 cases and non-dyslipidemias 122 cases) and 286 cases of control group was conducted in the Erqi district of Zhengzhou and Wuzhi county of Jiaozuo. The subjects accepted questionnaire survey, physical measurement, and blood sample collection. The blood samples were used to measure the lipid profiles and detect the Vitamin D receptor(VDR) gene ApaⅠ(rs7975232, G>T) and TaqⅠ(rs731236, T>C) polymorphisms. The content of questionnaire survey included age, gender, family history, dietary survey, physical activity and so on. The concentrations of total cholesterol(TC), triglycerides(TG), high density lipoprotein cholesterol(HDL-C), and low density lipoprotein cholesterol(LDL-C) in serum were determined by automatic biochemical analyzer. The gene polymorphisms were genotyped by using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). These differences of the gene polymorphisms and the corresponding clinical data were analyzed according to these results. Haplotype was analyzed by SHEsis online software. Other statistical analyses were performed using the SPSS software, version 21.0. The significant level was set as α=0.05.Results 1. Body mass index(BMI), waist-to-hip ratio(WHR) and serum TG levels of the T2 DM group were higher than that of the control group, but the serum HDL-C level were lower, the differences were statistically significant(P<0.05). BMI, body fat content, WHR, serum TC, and TG levels in the subjects of dyslipidemias were higher, but the serum HDL-C and LDL-C levels were lower than that of the non-dyslipidemias, the differences were statistically significant(P<0.05).2. The difference of ApaⅠ allele frequency distribution between the T2 DM group3. and the control group was statistically significant(χ2=4.572, P=0.032, OR=1.338, 95% CI: 1.024~1.749). The frequency distribution of genotype GG and GT+TT between the T2 DM group and the control group had statistical significance(χ2=4.311, P=0.038, OR=1.422, 95%CI: 1.019~1.983). There were no significant differences in the genotype frequency or allele distribution of TaqⅠin these two groups(P>0.05). There were statistically significant distributional differences of haplotype GT(ApaⅠ-TaqⅠ) and TT(ApaⅠ-TaqⅠ) between T2 DM group and control group, the haplotype GT(ApaⅠ-TaqⅠ) may statistically associate with the reduction of T2 DM risk(OR=0.756, 95% CI: 0.579~0.989), and the haplotype TT(ApaⅠ-TaqⅠ) may associate with the rise of T2 DM risk(OR=1.491, 95% CI: 1.116~1.992).4. Body fat content(F=4.464, P=0.012) and LDL-C level(F=3.795, P=0.023) of each ApaⅠ genotype(GG/GT/TT) was statistically different. Among them, body fat content of the people with TT genotype was higher than that of those with GG(P=0.003) and those with GT(P=0.025), the LDL-C level of people with GG genotype was lower than that of people with GT(P=0.006). all index levels had no statistically significant distributional differences between each Taq Ⅰ genotype(TT/TC/CC)(P>0.05).5. The logistic regression analysis suggested: as a reference to control group, the significant variables were physical activity(OR=0.754, 95%CI: 0.623~0.912), WHR increase(OR=2.087, 95%CI: 1.221~3.568) and ApaⅠGT+TT genotypes(OR=1.468, 95%CI: 1.042~2.067). As a reference to non-dyslipidemias group, the significant variable was WHR increase(OR=2.479, 95%CI: 1.064~5.775).Conclusions 1. The population with T2 DM in this study have a certain degree of lipid metabolic disorders, including the increased TG level and reduced HDL-C level.2. In this sudy, physical activity is the protective factor in T2DM; WHR increase is the risk factor of T2 DM and dyslipidemia. In order to reduce the risk of dyslipidemia, the patients with T2 DM should have reasonable diet, moderate exercise and healthy weight.3. In this sudy, VDR gene ApaⅠ polymorphism is associated with T2 DM, T allel isa susceptible gene of T2 DM. The haploid GT(ApaⅠ-TaqⅠ) is a protective factor for T2 DM, but haploid TT(ApaⅠ-TaqⅠ) is a risk factor for T2 DM. VDR gene ApaⅠ and TaqⅠ polymorphism has no correlation with dyslipidemia, the VDR gene ApaⅠ and TaqⅠ are not the susceptible genes for dyslipidemia.