Association Of Vitamin D Receptor Gene Polymorphisms With Diabetic Dyslipidemia And Essential Hypertension Disease In Elderly Male Patients

Part OneAssociation of VDR-gene variants with factors related to diabetic dyslipidemia of elderly male populationObjective:Diabetes mellitus (DM) was known as complex disease manifested by both genetic and one of the highest prevalence diseases. The interaction between diabetes and dyslipidemia, will promotes the progress of diabetic vascular disease and atherosclerosis. And diabetic vascular disease is highly associated with atherosclerosis caused by dyslipidemia. Cardiovascular disease is the main cause of death in patients with diabetes. Vitamin D receptor (VDR) gene polymorphism is associated with insulin secretion, and is the candidate gene of diabetes. The mechanism of diabetic dyslipidemia is very complicated. The aim of the present report was to study polymorphism of VDR gene and their involvement in the genetic predisposition to type 2 diabetic dyslipidemia in the elderly male of Beijing Han population.Methods:Three-hundred-twenty-eight Chinese Han individuals (237 DM and 91 controls) were enrolled in this case-control study. The DM group was divided into Non-Dyslipidemia group (DO group) including 134 patients and Dyslipidemia group (DH group) including 103 patients. FokI, BsmI, ApaI and TaqI single nucleotide polymorphism (SNP) of the VDR gene were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, DNA sequencing technology, and compared with their clinical characteristics.Results:Because the allele frequencies of VDR FokI, BsmI, Apal and TaqI related sites distribution obeys the Hardy-Weinberg law, there was a good representative. The level of FokI site C allele frequency in the DM group was significantly higher than that in NC group (x2=3.873, p=0.049, OR=1.439,95%CI:1.001-2.071). In the FokI dominant model, the frequency of CC genotype in DM group was obviously higher than that in NC group (x2=5.057,p=0.025, OR=1.756,95%CI:1.072-2.875), the frequency of CC genotype in DH group was obviously higher than that in NC group (x2=6.168, p=0.013, OR=2.06,95%CI:1.161-3.663); there was no significant differences in the genotype frequency or allele distribution in other paired groups (p>0.05). B No significant difference was detected in genotype frequency or allele distribution of BsmI, Apal and TaqI polymorphisms between the groups (p>0.05). In FokI, compared to CT+TT genotype, diastolic blood pressure in CC genotype was significantly lower,2h glucose, triglycerides, creatinine and uric acid levels were higher in CC genotype, and the difference was statistically significant (p=0.039; 0.035; 0.049; 0.047; 0.031). The level of serum creatinine in AA+AG genotype of BsmI was significantly lower than that of GG genotype, the difference was statistically significant (p=0.011). Unconditional logistic regression analysis revealed that FokI genotype, BMI, SBP, and smoking were risk factors for DH (CC genotype OR= 1.866,95%CI:1.007-3.458,^=0.047).Conclusion:VDR gene FokI polymorphisms may be a risk factor for dyslipidemia in elderly male patients with type 2 diabetes among Chinese Han population, where BsmI, Apal and TaqI polymorphisms are not associated with diabetic dyslipidemia.Part TwoRelationship between vitamin D receptor gene polymorphism and essential hypertension in elderly male patientsObjective:Essential hypertension (EHT) was known as polygenic disease by the interaction between genetic factors and environmental factors. Vitamin D receptor (VDR) gene polymorphism is associated with plasma renin activity. The aim of the present report was to study polymorphism of VDR gene and their involvement in the genetic predisposition to essential hypertension in the elderly male of Beijing Han population, in order to provide clinical basis for the study of molecular mechanism between VDR gene and hypertension.Methods:Four hundred and twelve Chinese Han individuals (228 EHT and 184 controls) were enrolled in this case-control study. FokI, BsmI, ApaI and TaqI single nucleotide polymorphism (SNP) of the VDR gene were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, DNA sequencing technology, and compared with their clinical characteristics.Results:All SNPs complied with Hardy-Weinberg equilibrium distributions. At the FokI locus, the C allele frequency in EHT group was significantly higher than that in NC group (χ2=3.859,p=0.049, OR=1.347,95%CI:1.000-1.815). In the recessive model, CC+CT genotype frequency was significantly higher in EHT group than that in NC group (χ2=4.320, p=0.038, OR=2.076,95%CI:1.030-4.182). The three loci genotype and allele frequencies of BsmI, ApaI and TaqI were not significantly different between groups (p>0.05). Unconditional logistic regression analysis revealed that Fokl genotype was risk factor for EHT of elderly male patients (CC+CT genotype OR= 2.054,95%CI=1.003-4.204,p=0.049).Conclusions:VDR gene FokI polymorphism may be a risk factor for elderly male patients with essential hypertension, but no association was detected between BsmI, ApaI, and TaqI polymorphisms and essential hypertension in elderly male.