【摘要】：目的探討維生素D和維生素D受體(Vitamin D receptor, VDR)基因多態(tài)性與2型糖尿病(type 2 diabetes mellitus, T2DM)的關(guān)系,以及基因-環(huán)境交互作用對2型糖尿病發(fā)生的影響。方法根據(jù)研究設(shè)計,采用病例對照研究方法,于2013年1月-2013年5月在河南省鄭州市侯寨鄉(xiāng)和焦作市喬廟鄉(xiāng)收集286例2型糖尿病患者作為T2DM組,然后按1：1比例選擇286例與T2DM組人群同性別、年齡±5歲、無相關(guān)慢性病的同地區(qū)人群為對照組。對兩組人群進(jìn)行問卷調(diào)查及體格檢查,同時收集空腹靜脈血。采用全自動生化分析儀測定血清中總膽固醇、甘油三酯、高密度脂蛋白水平；采用酶聯(lián)免疫吸附法(Enzyme linked immunosorbent assay, ELISA)測定血清中25(OH)D3和1,25(OH)2D3水平。利用TaqMan探針法分析VDR基因rs2189480和rs3847987兩個位點的多態(tài)性。運用Haplo.stats軟件包分析單體型,采用多因子降維模型(]multifactor dimensionality reduction, MDR)分析基因-環(huán)境交互作用,其余數(shù)據(jù)采用SPSS21.0軟件分析,檢驗水準(zhǔn)a=0.05。結(jié)果1.VDR基因多態(tài)性與2型糖尿病的關(guān)系攜帶rs2189480位點純合基因型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型糖尿病的發(fā)病風(fēng)險。攜帶rs3847987位點等位基因A (OR=1.457,95% CI:1.085,1.957)可能增加2型糖尿病的發(fā)病風(fēng)險。攜帶單體型CC (rs2189480-rs3847987)可能降低2型糖尿病的發(fā)病風(fēng)險(OR=0.729,95% CI:0.543,0.978)。2.血清維生素D水平與2型糖尿病T2DM組和對照組人群血清25(OH)D3水平分別為32.33±33.18、38.87±41.00ng/ml,1,25(OH)2D3水平分別為31.07±40.39、42.78±58.41pg/ml,T2DM組人群血清25(OH)D3和1,25(OH)2D3水平明顯低于對照組,差異有統(tǒng)計學(xué)意義(分別P0.05)。以VDR基因型進(jìn)行分層,結(jié)果顯示T2DM組攜帶rs2189480 CA基因型和rs3847987 CC基因型人群血清25(OH)D3和1,25(OH)2D3水平明顯低于對照組,差異有統(tǒng)計學(xué)意義(分別P0.05)。對體力活動、是否有2型糖尿病家族史分層,T2DM組無2型糖尿病家族史人群血清25(OH)D3水平明顯低于對照組,差異有統(tǒng)計學(xué)意義(P0.05)。輕度體力活動、重度體力活動和無2型糖尿病家族史人群T2DM組1,25(OH)2D3水平均明顯低于對照組,差異有統(tǒng)計學(xué)意義(分別P0.05)。3.基因-環(huán)境交互作用對2型糖尿病的影響分析結(jié)果顯示,rs2189480、rs3847987和體力活動三者對2型糖尿病的影響存在交互作用(OR=2.53,95% CI:1.81,3.54)。結(jié)論1.VDR基因rs2189480和rs3847987位點多態(tài)性與2型糖尿病發(fā)病風(fēng)險相關(guān),上述兩個位點單體型CC與2型糖尿病發(fā)病風(fēng)險降低有關(guān)。2.2型糖尿病患者血清維生素D (25(OH)3、1,25(OH)2D3)水平明顯降低。3. rs2189480、rs3847987和體力活動三者在2型糖尿病的發(fā)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 鹵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 鹵33.188.87 鹵41.00 ng / ml ~ (-1) (OH) 2D3 in T2DM group and 31.07 鹵40.39 鹵42.78 鹵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.
【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R587.1

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本文編號：2221179