【摘要】：目的:觀察中國泰安市漢族人群乙醛脫氫酶2(ALDH2)基因第12外顯子單核酸多態(tài)性(Glu504Lys)分布情況,探討ALDH2基因多態(tài)性與糖尿病腎病并發(fā)冠心病的關(guān)聯(lián)性。方法:采用病例-對照研究方法。將305例受試對象分為三組;分別為對照組(A組)、糖尿病腎病組(B組)和糖尿病腎病并發(fā)冠心病組(C組)。其中A組:124例,男性65例,女性59例,平均年齡52.13±9.38歲;B組:85例,男性44例,女性41例,平均年齡50.97±7.40歲;C組:96例,男性49例,女性47例,平均年齡59.95±10.71歲。A組來自中國人民解放軍88醫(yī)院2011年3月至2013年12月職工健康查體者,B組和C組均來自同期中國人民解放軍88醫(yī)院住院患者,所有受試者之間均無血緣關(guān)系。發(fā)放調(diào)查表,所有受試對象填寫相關(guān)的一般資料,包括年齡,性別,飲酒行為(飲酒量+飲酒頻率)、體重指數(shù)等。常規(guī)抽取靜脈血,平行做血液生化檢查和基因型分析。生化檢查項目包括血糖、胰島素、血尿酸、膽固醇和甘油三酯等。基因型分析先提取外周血基因組DNA,以之為模板做PCR(polymerase chain reaetion,聚合酶鏈?zhǔn)椒磻?yīng)),DNA微陣列法分析ALDH2基因多態(tài)性,記錄各個體基因型,用SPSS13.0軟件進行統(tǒng)計分析。結(jié)果:(l)ALDH2基因Glu504Lys多態(tài)性基因型分布均符合Hardy-Weinberg遺傳平衡定律。(2)ALDH2基因Glu504Lys多態(tài)性基因型Glu504Glu、Glu504Lys和Lys504Lys從分布情況:對照組(A組)三種基因型個體的百分比分別為59.38%、29.56%和5.14%;糖尿病腎病組(B組)三種基因型個體的百分比分別為52.59%、38.50%和6.04%、糖尿病腎病合并冠心病組(C組)三種基因型個體的百分比分別為42.39%、47.89%和7.82%。其中,A組與B組無差別,C組突變等位基因雜合體及純合體基因型(Glu504Lys和Lys504Lys)頻率高于A/B兩組(P0.01)。(3)糖尿病腎病并發(fā)冠心病的二元Logistic回歸分析,ALDH2基因Glu504Lys多態(tài)性、吸煙、體重指數(shù)、年齡和血尿酸進入方程;攜帶突變等位基因的基因型較之Glu504Glu基因型者,糖尿病腎病并發(fā)冠心病危險性增高,其比數(shù)比為3.293(95%可信區(qū)間為1.458-7.440)。伴有心血管危險因素越多的糖尿病腎病患者攜帶突變等位基因的基因型(Glu504Lys和Lys504Lys)頻率越高(P0.05)。(4)攜帶突變等位基因并伴有高胰島素血癥的患者其收縮壓、舒張壓和平均動脈壓均升高(P0.05)。結(jié)論:中國泰安漢族人群存在ALDH2基因第12外顯子單核苷酸多態(tài)性(Glu504Lys);ALDH2基因Glu504Lys多態(tài)性在病例組與對照組間的基因型與等位基因頻率有統(tǒng)計學(xué)差異,提示該位點與中國泰安漢族人群糖尿病腎病合并冠心病的有相關(guān)性。有ALDH2基因Glu504Lys突變多態(tài)位點的個體常伴有高胰島素血癥者收縮壓、舒張壓和平均動脈壓升高,提示該位點是糖尿病腎病合并冠心病的危險因素。這部分人群存在更加嚴(yán)重的多代謝紊亂,推進心血管事件鏈由起點向終點不斷進展。
[Abstract]:Aim: to investigate the distribution of single nucleic acid polymorphism (Glu504Lys) in exon 12 of aldehyde dehydrogenase 2 (ALDH2) gene in Tai'an Han population, and to explore the relationship between ALDH2 gene polymorphism and diabetic nephropathy complicated with coronary heart disease. Methods: a case-control study was used. 305 subjects were divided into three groups: control group (group A), diabetic nephropathy group (group B) and diabetic nephropathy complicated with coronary heart disease group (group C). There were 124 cases in group A, 65 males and 59 females, with an average age of 52.13 鹵9.38 years old in group B: 85, 44 males and 41 females, with an average age of 50.97 鹵7.40 years old in group C: 96, 49 males and 47 females. The average age of group A was 59.95 鹵10.71 years old. Group A came from Chinese PLA 88 Hospital from March 2011 to December 2013. Both group B and group C came from inpatients in 88 Hospital of PLA. There was no blood relationship among all subjects. Questionnaires were given to all subjects, including age, sex, drinking behavior (alcohol consumption frequency), body mass index (BMI) and so on. Routine venous blood was drawn and blood biochemical examination and genotype analysis were carried out in parallel. Biochemical tests include blood sugar, insulin, uric acid, cholesterol and triglycerides. PCR (polymerase chain reaetion, polymerase chain reaction (PCR (polymerase chain reaetion, polymerase chain reaction) was used as a template to analyze the polymorphism of ALDH2 gene by genotypic analysis. The genotypes of each individual were recorded and analyzed by SPSS13.0 software. Results: the distribution of Glu504Lys polymorphism genotypes of (l) ALDH2 gene was in accordance with the law of Hardy-Weinberg genetic balance. (2) the distribution of Glu504Glu504Lys and Lys504Lys genotypes of ALDH2 gene Glu504Lys polymorphism: the percentages of the three genotypes in the control group (group A) were 59.38% and 5.14%, respectively, and that in diabetic kidney were 59.38% and 5.14%, respectively. The percentages of the three genotypes in the disease group (group B) were 38.50% and 6.04, respectively, and the percentages of the three genotypes in the diabetic nephropathy with coronary heart disease group (group C) were 42.39% and 7.82%, respectively. The frequency of allele heterozygote and homozygous genotype (Glu504Lys and Lys504Lys) in group A and group B were higher than those in group A and group B (P0.01). (3). The Glu504Lys polymorphism of ALDH2 gene, smoking and body mass index (BMI) in diabetic nephropathy complicated with coronary heart disease (CHD) were significantly higher than those in group A (P0.01). (3). Age and serum uric acid entered the equation, the genotype with mutation allele was higher than Glu504Glu genotype in the risk of diabetic nephropathy complicated with coronary heart disease, the specific ratio was 3.293 (95% confidence interval 1.458-7.440). The higher the frequency of Glu504Lys and Lys504Lys in diabetic nephropathy patients with more cardiovascular risk factors (P0.05). (4), the higher systolic blood pressure, diastolic blood pressure and mean arterial pressure in patients with hyperinsulinemia (P0.05). Conclusion: the single nucleotide polymorphisms (Glu504Lys) of ALDH2 gene exon 12 and ALDH2 gene Glu504Lys polymorphisms exist in the Han population of Tai'an, China. There is a significant difference in genotype and allele frequency between the case group and the control group. The results suggest that this locus is associated with diabetic nephropathy and coronary heart disease in Tai'an Han nationality. Individuals with polymorphic loci of Glu504Lys mutation of ALDH2 gene were often associated with hyperinsulinemia with elevated systolic blood pressure, diastolic blood pressure and mean arterial pressure, suggesting that this locus was a risk factor for diabetic nephropathy with coronary heart disease. There are more serious multiple metabolic disorders in this population, and the cardiovascular event chain progresses from starting point to end point.
【學(xué)位授予單位】：泰山醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R587.2;R541.4;R692.9

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