ALDH2基因多态性与泰安人群糖尿病肾病并发冠心病的相关性研究

发布时间：2018-08-10 21:39

【摘要】：目的:观察中国泰安市汉族人群乙醛脱氢酶2(ALDH2)基因第12外显子单核酸多态性(Glu504Lys)分布情况,探讨ALDH2基因多态性与糖尿病肾病并发冠心病的关联性。方法:采用病例-对照研究方法。将305例受试对象分为三组;分别为对照组(A组)、糖尿病肾病组(B组)和糖尿病肾病并发冠心病组(C组)。其中A组:124例,男性65例,女性59例,平均年龄52.13±9.38岁;B组:85例,男性44例,女性41例,平均年龄50.97±7.40岁;C组:96例,男性49例,女性47例,平均年龄59.95±10.71岁。A组来自中国人民解放军88医院2011年3月至2013年12月职工健康查体者,B组和C组均来自同期中国人民解放军88医院住院患者,所有受试者之间均无血缘关系。发放调查表,所有受试对象填写相关的一般资料,包括年龄,性别,饮酒行为(饮酒量+饮酒频率)、体重指数等。常规抽取静脉血,平行做血液生化检查和基因型分析。生化检查项目包括血糖、胰岛素、血尿酸、胆固醇和甘油三酯等。基因型分析先提取外周血基因组DNA,以之为模板做PCR(polymerase chain reaetion,聚合酶链式反应),DNA微阵列法分析ALDH2基因多态性,记录各个体基因型,用SPSS13.0软件进行统计分析。结果:(l)ALDH2基因Glu504Lys多态性基因型分布均符合Hardy-Weinberg遗传平衡定律。(2)ALDH2基因Glu504Lys多态性基因型Glu504Glu、Glu504Lys和Lys504Lys从分布情况:对照组(A组)三种基因型个体的百分比分别为59.38%、29.56%和5.14%;糖尿病肾病组(B组)三种基因型个体的百分比分别为52.59%、38.50%和6.04%、糖尿病肾病合并冠心病组(C组)三种基因型个体的百分比分别为42.39%、47.89%和7.82%。其中,A组与B组无差别,C组突变等位基因杂合体及纯合体基因型(Glu504Lys和Lys504Lys)频率高于A/B两组(P0.01)。(3)糖尿病肾病并发冠心病的二元Logistic回归分析,ALDH2基因Glu504Lys多态性、吸烟、体重指数、年龄和血尿酸进入方程;携带突变等位基因的基因型较之Glu504Glu基因型者,糖尿病肾病并发冠心病危险性增高,其比数比为3.293(95%可信区间为1.458-7.440)。伴有心血管危险因素越多的糖尿病肾病患者携带突变等位基因的基因型(Glu504Lys和Lys504Lys)频率越高(P0.05)。(4)携带突变等位基因并伴有高胰岛素血症的患者其收缩压、舒张压和平均动脉压均升高(P0.05)。结论:中国泰安汉族人群存在ALDH2基因第12外显子单核苷酸多态性(Glu504Lys);ALDH2基因Glu504Lys多态性在病例组与对照组间的基因型与等位基因频率有统计学差异,提示该位点与中国泰安汉族人群糖尿病肾病合并冠心病的有相关性。有ALDH2基因Glu504Lys突变多态位点的个体常伴有高胰岛素血症者收缩压、舒张压和平均动脉压升高,提示该位点是糖尿病肾病合并冠心病的危险因素。这部分人群存在更加严重的多代谢紊乱,推进心血管事件链由起点向终点不断进展。
[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 卤9.38 years old in group B: 85, 44 males and 41 females, with an average age of 50.97 卤7.40 years old in group C: 96, 49 males and 47 females. The average age of group A was 59.95 卤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.
【学位授予单位】：泰山医学院
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R587.2;R541.4;R692.9

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