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福建漢族人群TCF7L2基因多態(tài)性、機(jī)體及環(huán)境因素與2型糖尿病關(guān)聯(lián)性研究

發(fā)布時間:2018-05-23 23:42

  本文選題:2型糖尿病 + 病例對照研究 ; 參考:《福建醫(yī)科大學(xué)》2015年碩士論文


【摘要】:目的探討TCF7L2基因多態(tài)性與2型糖尿病(type 2 diabetes,T2DM)的關(guān)聯(lián)性,篩選T2DM的環(huán)境影響因素及機(jī)體因素,探討TCF7L2基因多態(tài)與機(jī)體及環(huán)境因素之間交互作用對T2DM的影響。研究方法采用1:1病例對照研究方法,選擇福建省的5個國家疾病監(jiān)測點的社區(qū)人群中T2DM患者為病例,選擇與病例同性別、同居住地、同民族、年齡相差小于5歲的非糖尿病的人群為對照。對進(jìn)入研究的596名對象進(jìn)行環(huán)境因素的調(diào)查,體格測量和血清學(xué)指標(biāo)的檢測,并提取血樣DNA,應(yīng)用Mass ARRAY技術(shù)檢測TCF7L2基因上的10個SNPs位點(rs11196205、rs12255372、rs4506565、rs7901695、rs7903146、rs7895340、rs11196218、rs12775879、rs290481、rs6585205)的基因型。采用Epidate3.1軟件建立數(shù)據(jù)庫,SHEsis軟件分析基因型及單體型。GMDR.09軟件分析構(gòu)建TCF7L2基因各SNP位點、基因-環(huán)境及機(jī)體因素交互作用模型,其余統(tǒng)計分析采用SPSS 18.0軟件。研究結(jié)果共有596名研究對象參加了研究,T2DM病例和對照各298例,婚姻、教育程度在兩組間的分布沒有統(tǒng)計學(xué)差異。1.TCF7L2基因多態(tài)與T2DM的關(guān)系TCF7L2基因各SNP位點的基因型分布均符合Hardy-Weinberg遺傳平衡檢驗;尚未發(fā)現(xiàn)TCF7L2基因各SNP位點與T2DM相關(guān);尚未發(fā)現(xiàn)TCF7L2基因各SNP位點構(gòu)建的單體型與T2DM相關(guān)。2.血清學(xué)、體格測量指標(biāo)與T2DM的關(guān)系Hs-CRP、TC、HDL-C、TG、Hb A1c、SBP、DBP、BMI、WC各指標(biāo)檢測水平病例組均顯著高于對照組(P0.050),與T2DM密切相關(guān)。3.T2DM的危險因素篩選出T2DM的危險因素有:吸煙(OR=1.702,OR95%CI=1.029-2.813),飲酒(OR=1.963,OR95%CI=1.246-3.093),向心性肥胖(OR=2.348,OR95%CI=1.591-3.465),高血壓疾病史(OR=2.219,OR95%CI=1.379-3.288)和血脂異常疾病史(OR=2.730,OR95%CI=1.323-5.633);保護(hù)因素為是食用新鮮水果(OR=0.679,OR95%CI=0.297-0.969)。4.TCF7L2基因、機(jī)體及環(huán)境因素交互作用與T2DM的關(guān)系向心性肥胖對T2DM的影響為主效應(yīng)因素;向心性肥胖與吸煙存在負(fù)相加交互作用;病例組HOMA-β在rs290481位點的三種基因分型中均具有統(tǒng)計學(xué)意義。結(jié)論5.1本次研究尚未發(fā)現(xiàn)TCF7L2基因10個SNPs多態(tài)性與T2DM相關(guān);尚未發(fā)現(xiàn)TCF7L2基因的10個SNPs構(gòu)建的單體型與T2DM存在關(guān)聯(lián);5.2本次研究發(fā)現(xiàn)吸煙、飲酒、向心性肥胖、高血壓疾病史、高血脂疾病史是福建漢族人群T2DM的危險因素,食用新鮮水果是保護(hù)因素;5.3向心性肥胖在TCF7L2基因、機(jī)體及環(huán)境因素對T2DM的影響中起主要作用;5.4 TCF7L2基因rs290481多態(tài)可能影響胰島素的分泌。
[Abstract]:Objective to investigate the association between TCF7L2 gene polymorphism and type 2 diabetes mellitus (T2DM), to screen the environmental and body factors of T2DM, and to explore the effect of TCF7L2 gene polymorphism on T2DM. Methods the 1:1 case-control study was used to select the T2DM patients in the community population of five national disease surveillance sites in Fujian Province, and choose the same sex, same place of residence, same nationality as the case. Non-diabetic subjects with age differences of less than 5 years were controls. A total of 596 subjects were investigated for environmental factors, physical measurements and serological indices, and blood DNA samples were extracted. The genotypes of 10 SNPs loci rs12255372rs4506565rs79031465rs79031465rs11196218rs127758791rs290481rs6585205 were detected by Mass ARRAY technique. The TCF7L2 gene SNP loci, gene-environment and organism interaction models were constructed by using Epidate3.1 software to establish a database for genotype analysis and haplotype. GMDR.09 software was used to analyze the genotype and haplotype. The other statistical analysis software was SPSS 18.0. The results showed that a total of 596 subjects took part in the study of T2DM cases and 298 controls each. There was no statistical difference in the distribution of educational level between the two groups. 1. The relationship between the polymorphism of TCF7L2 gene and T2DM the genotype distribution of SNP loci of TCF7L2 gene all accord with the Hardy-Weinberg genetic balance test, the SNP loci of TCF7L2 gene were not found to be associated with T2DM. Haplotypes constructed at SNP sites of TCF7L2 gene have not been found to be related to T2DM. Serology, The relationship between physical parameters and T2DM: Hs-CRPU TCU HDL-Cn TGG HbA1cBMI-WC level was significantly higher than that of control group P0.0500.The risk factors of T2DM closely related to T2DM were as follows: smoking OR1.702OR95CI1.02.813C, alcohol drinking OR1.963OR95CIT 1.246-3.093C, heart obesity OR2.348OR9595 CIQ 1.591-3.4655.The risk factors of T2DM were as follows: smoking OR1.702OR95CI1.02.2.963CIT 1.246-3.093C, and heart obesity OR2.348OR9595. The risk factors of T2DM were 1.591-3.4650.The risk factors of T2DM were as follows: smoking OR1.702O95CI1.02.8130.The alcohol drinking OR1.963OR95CII was 1.246-3.093C, and the risk factors were 1.591-3.465. The disease history is 2.219 / OR95CIN 1.379-3.288) and the history of dyslipidemia is 2.730 / OR95CIQ 1.323-5.633. The protective factors are the consumption of fresh fruit OR0.679, OR95CIN 0.297-0.969C, and 4.TCF7L2 gene. The relationship between the interaction of body and environment factors and T2DM; the negative additive interaction between concentric obesity and smoking; and the significant difference of HOMA- 尾 in the three genotypes of rs290481 locus. Conclusion in this study, 10 SNPs polymorphisms of TCF7L2 gene were not found to be associated with T2DM, and haplotypes constructed by 10 SNPs of TCF7L2 gene were not found to be associated with T2DM. The history of hyperlipidemia is a risk factor for T2DM in Fujian Han population, and eating fresh fruit is a protective factor in TCF7L2 gene. The effect of body and environment factors on T2DM may play a major role in the effect of rs290481 polymorphism of TCF7L2 gene on insulin secretion.
【學(xué)位授予單位】:福建醫(yī)科大學(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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