维生素D、维生素D受体基因多态性与2型糖尿病的关系

发布时间：2018-09-04 05:41

【摘要】：目的探讨维生素D和维生素D受体(Vitamin D receptor, VDR)基因多态性与2型糖尿病(type 2 diabetes mellitus, T2DM)的关系,以及基因-环境交互作用对2型糖尿病发生的影响。方法根据研究设计,采用病例对照研究方法,于2013年1月-2013年5月在河南省郑州市侯寨乡和焦作市乔庙乡收集286例2型糖尿病患者作为T2DM组,然后按1：1比例选择286例与T2DM组人群同性别、年龄±5岁、无相关慢性病的同地区人群为对照组。对两组人群进行问卷调查及体格检查,同时收集空腹静脉血。采用全自动生化分析仪测定血清中总胆固醇、甘油三酯、高密度脂蛋白水平；采用酶联免疫吸附法(Enzyme linked immunosorbent assay, ELISA)测定血清中25(OH)D3和1,25(OH)2D3水平。利用TaqMan探针法分析VDR基因rs2189480和rs3847987两个位点的多态性。运用Haplo.stats软件包分析单体型,采用多因子降维模型(]multifactor dimensionality reduction, MDR)分析基因-环境交互作用,其余数据采用SPSS21.0软件分析,检验水准a=0.05。结果1.VDR基因多态性与2型糖尿病的关系携带rs2189480位点纯合基因型CC (OR=0.448,95% CI:0.256,0.786)和等位基因C (OR=0.753,95% CI:0.589,0.962)能降低2型糖尿病的发病风险。携带rs3847987位点等位基因A (OR=1.457,95% CI:1.085,1.957)可能增加2型糖尿病的发病风险。携带单体型CC (rs2189480-rs3847987)可能降低2型糖尿病的发病风险(OR=0.729,95% CI:0.543,0.978)。2.血清维生素D水平与2型糖尿病T2DM组和对照组人群血清25(OH)D3水平分别为32.33±33.18、38.87±41.00ng/ml,1,25(OH)2D3水平分别为31.07±40.39、42.78±58.41pg/ml,T2DM组人群血清25(OH)D3和1,25(OH)2D3水平明显低于对照组,差异有统计学意义(分别P0.05)。以VDR基因型进行分层,结果显示T2DM组携带rs2189480 CA基因型和rs3847987 CC基因型人群血清25(OH)D3和1,25(OH)2D3水平明显低于对照组,差异有统计学意义(分别P0.05)。对体力活动、是否有2型糖尿病家族史分层,T2DM组无2型糖尿病家族史人群血清25(OH)D3水平明显低于对照组,差异有统计学意义(P0.05)。轻度体力活动、重度体力活动和无2型糖尿病家族史人群T2DM组1,25(OH)2D3水平均明显低于对照组,差异有统计学意义(分别P0.05)。3.基因-环境交互作用对2型糖尿病的影响分析结果显示,rs2189480、rs3847987和体力活动三者对2型糖尿病的影响存在交互作用(OR=2.53,95% CI:1.81,3.54)。结论1.VDR基因rs2189480和rs3847987位点多态性与2型糖尿病发病风险相关,上述两个位点单体型CC与2型糖尿病发病风险降低有关。2.2型糖尿病患者血清维生素D (25(OH)3、1,25(OH)2D3)水平明显降低。3. rs2189480、rs3847987和体力活动三者在2型糖尿病的发生中存在交互作用。
[Abstract]:Objective to investigate the relationship between vitamin D and vitamin D receptor (Vitamin D receptor, VDR) gene polymorphism and type 2 diabetes mellitus (type 2 diabetes mellitus, T2DM) and the effect of gene-environment interaction on type 2 diabetes mellitus. Methods from January 2013 to May 2013, 286 patients with type 2 diabetes mellitus were collected as T2DM group in Houzhai Township, Zhengzhou City, Henan Province and Qiaomiao Township, Jiaozuo City, from January 2013 to May 2013. Then, according to the 1:1 ratio, 286 cases of the same sex, age 卤5 years old and no related chronic diseases were selected as the control group with the same sex as the T2DM group. The two groups were investigated by questionnaire and physical examination, and fasting venous blood was collected at the same time. Total cholesterol, triglyceride and high density lipoprotein in serum were measured by automatic biochemical analyzer, and 25 (OH) D 3 and 1 25 (OH) 2D3 in serum were determined by enzyme linked immunosorbent assay (Enzyme linked immunosorbent assay, ELISA). The polymorphism of rs2189480 and rs3847987 loci of VDR gene was analyzed by TaqMan probe method. The haplotype was analyzed by Haplo.stats software package, and the interaction between gene and environment was analyzed by multi-factor dimensionality reduction model (multifactor dimensionality reduction, MDR). The other data were analyzed by SPSS21.0 software. Results 1.VDR gene polymorphism was associated with type 2 diabetes mellitus. Homozygous genotype CC (OR=0.448,95% CI:0.256,0.786) and allele C (OR=0.753,95% CI:0.589,0.962) at rs2189480 locus could reduce the risk of type 2 diabetes mellitus. Carrying rs3847987 allele A (OR=1.457,95% CI:1.085,1.957) may increase the risk of type 2 diabetes. Carrying haplotype CC (rs2189480-rs3847987) may reduce the risk of type 2 diabetes (OR=0.729,95% CI:0.543,0.978. 2. 2). The levels of serum vitamin D were 32.33 卤33.188.87 卤41.00 ng / ml ~ (-1) (OH) 2D3 in T2DM group and 31.07 卤40.39 卤42.78 卤58.41 PG / ml / T _ (2) DM group respectively. The serum 25 (OH) D _ 3 and 25 (OH) 2D3 levels in type 2 diabetes mellitus group were significantly lower than those in control group (P 0.05). The serum levels of 25 (OH) D3 and 1C25 (OH) 2D3 in T2DM group with rs2189480 CA genotype and rs3847987 CC genotype were significantly lower than those in control group (P0.05). For physical activity, the serum level of 25 (OH) D3 in T2DM group without type 2 diabetes family history was significantly lower than that in control group, the difference was statistically significant (P0.05). The level of 1o 25 (OH) 2D3 in T2DM group was significantly lower than that in control group in mild physical activity, severe physical activity and no family history of type 2 diabetes (P0.05). The effects of gene-environment interaction on type 2 diabetes mellitus were analyzed. The results showed that there was interaction between rs2189480 rs3847987 and physical activity on type 2 diabetes mellitus (OR=2.53,95% CI:1.81,3.54). Conclusion the polymorphism of rs2189480 and rs3847987 loci of 1.VDR gene is associated with the risk of type 2 diabetes mellitus. The haplotype CC at the above two loci was associated with a decrease in the risk of type 2 diabetes mellitus. The serum vitamin D (25 (OH) 3tir 25 (OH) 2D3) levels were significantly decreased in type 2 diabetic patients. There was interaction between rs2189480,rs3847987 and physical activity in the development of type 2 diabetes.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R587.1

【参考文献】