【作者】 张晨君；

【导师】 何秉贤；

【作者基本信息】 新疆医科大学 ， 内科学， 2009， 博士

【摘要】 目的:探讨维吾尔族、汉族糖尿病合并冠心病患者、冠心病患者、糖尿病患者血脂、血糖、体重指数等常见危险因素的分布情况,同时探讨载脂蛋白A5(APOA5)、载脂蛋白B(APOB)、胆固醇脂转运蛋白(CETP)基因多态性在前述各组中的分布特点及在汉族、维吾尔族之间的差异,并进一步明确APOA5、APOB、CETP基因多态性对汉族、维吾尔族冠心病、糖尿病、冠心病合并糖尿病患者的血脂代谢影响以及与上述疾病的关系。方法:选取2008年1月至2008年9月在心脏中心及内分泌科、干部综合内科住院的患者作为研究对象,冠心病患者266例,男性196例,女性70例;其中合并糖尿病154例,男性110例,女性44例;单纯糖尿病患者122例,其中男性84例,女性38例。对照组137例,其中男性77例,女性60例。测量身高、体重、血糖、血总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)、载脂蛋白A(APOA)、载脂蛋白B(APOB)、LPa等指标,计算载脂蛋白B/A比值,记录糖尿病病程、吸烟、年龄等,计算吸烟指数,进行不同组间比较,应用非条件Logistic回归分析糖尿病合并冠心病、冠心病、糖尿病发病的危险因素。同时提取白细胞基因组DNA,用聚合酶链反应(PCR)扩增和连接酶法检测CETP、APOA5、APOB基因多态性,分析汉族、维吾尔族基因型频率、等位基因频率的差别以及以上多态性与糖尿病合并冠心病的发病关系。结果:1)APOA5基因1131T/C分型提示:冠心病合并糖尿病组等位基因C携带者(CC+TC)TG水平及LP(a)明显高于C非携带者(TT);冠心病组(CHD)及冠心病合并糖尿病组(CHD+DM)的等位基因频率明显高于对照组,糖尿病组和对照组间C等位基因频率无统计学差异。病例组与对照组维吾尔族、汉族基因型频率之间无差别,但冠心病和糖尿病组维吾尔族C等位基因频率高于汉族。2) APOB基因EocRI多态性与血脂指标没有明显关联性,其中A等位基因频率虽然在冠心病组、糖尿病组高于对照组,但未达到统计学差异,在糖尿病合并冠心病组与对照组相同,A等位基因频率与冠心病发病率不存在一致性,冠心病组A等位基因频率最高,其次为糖尿病组、糖尿病合并冠心病组、对照组;病例组和对照组间A等位基因频率分布无显著性差异。冠心病合并糖尿病组A等位基因携带者BMI高于G等位基因携带者;冠心病组及冠心病合并糖尿病组维吾尔族GA基因型频率和等位基因频率高于汉族,而在糖尿病组中无差异;3) CETP基因D442G在四组人群中均未发现突变纯合子GG基因型,冠心病组CETP基因D442G突变频率为4.5%(5/112),冠心病合并糖尿病组突变率3.9%(6/154),糖尿病组突变率4.9%(6/122),而对照组突变频率为3.7%(5/136),病例组与对照组突变频率均无统计学意义(P＞0.05)。两组人群均符合Hardy-Weinberg平衡,具有群体代表性。维吾尔族和汉族G等位基因频率无统计学差异,DD和DG基因型在冠心病、冠心病合并糖尿病组的血脂水平比较无统计学差异;4)糖尿病组、冠心病组、糖尿病合并冠心病组TG、TC、LDL、APOB、血糖均高于对照组,达到统计学差异,P值＜0.05,三组之间年龄、BMI、HDL-C、LDL-C、APOA1、吸烟指数均有差别,其中糖尿病合并冠心病组更高于糖尿病组和冠心病组,但后两组间没有明显差别。冠心病组中维吾尔族HDL-C明显低于汉族,在糖尿病组中各项指标无明显差异。糖尿病合并冠心病组维吾尔族年龄均值低于汉族,BMI高于汉族。对照组内维吾尔族BMI、FBG、TG、APOB/A高于汉族。⑤年龄、BMI、TG、LDL-C、LP-a是冠心病的独立危险因素,女性是保护因素,其中LDL-C是最突出的危险因素。年龄、BMI、TC、LDL-C、LP-a是冠心病合并糖尿病的独立危险因素,女性、HDL-C是保护因素。年龄、TC、TG是糖尿病的独立危险因素。结论:APOA51131C等位基因可能与TG、LP-a升高有关,C等位基因可能是维吾尔族糖尿病合并冠心病的易感基因;APOB基因EocRI基因的A等位基因与血脂水平没有明显关系,A等位基因可能增加了维吾尔族糖尿病合并冠心病及冠心病的易感性;A等位基因可能是维吾尔族冠心病及冠心病合并糖尿病的易感基因;A等位基因与糖尿病合并冠心病腹型肥胖相关,与脂代谢相关。CETP基因D442G中GG纯合子突变极少见,G等位基因与血脂和糖尿病合并冠心病及冠心病、糖尿病的可能没有关系,维吾尔族该基因位点突变频率与汉族之间没有差异。高血脂、高血压、高血糖、体重指数升高是糖尿病合并冠心病的危险因素及冠心病的危险因素,高血压、高血脂、体重指数增加是糖尿病的危险因素。在健康人群中维吾尔族较汉族有更明显的脂代谢紊乱,糖尿病合并冠心病中,维吾尔族发病年龄较年轻。更多还原

【Abstract】 Objective:To investigate the Han,Uygur diabetes patients with coronary heart disease,coronary heart disease patients,diabetic patients with blood lipids,blood sugar, blood pressure and other common risk factors for the distribution,at the same time explore the APOA5,APOB,CETP gene polymorphisms with coronary heart disease in diabetes,and coronary heart disease,and diabetic patients distribution characteristics, clear whether there are differences,respectively,to explore and further define APOAS, APOB,CETP gene polymorphisms with the Han,Uygur coronary heart disease,diabetes, coronary heart disease associated with diabetes mellitus.Methods:from January 2008 to October 2008 in the heart center and inpatient endocrine patients as research subjects,266 cases of patients with coronary artery disease,196 cases of male,female 70 cases;one of 154 cases with diabetes,110 cases of male,female 44 cases;122 cases of patients with diabetes alone,one of 84 cases of male,female 38 cases.137 cases of the control group, one of 77 cases of male,female 60 cases.Measurement of height,weight,blood glucose, blood lipids,systolic blood pressure,diastolic blood pressure,blood total cholesterol, triglyceride,high density lipoprotein,low density lipoprotein and other indicators, Calculation of apolipoprotein B/A ratio and Smoking index calculation for different groups to compare,contrast,application of non-conditional Logistic regression analysis of diabetic patients with coronary heart disease,coronary heart disease,diabetes risk factors.At the same time,extracting leukocyte genomic DNA,respectively,by polymerase chain reaction(PCR) amplification and conection enzym method detection of CETP,APOA5,APOB gene polymorphism analysis of the above polymorphisms with coronary heart disease and diabetes incidence relations.Results:1) APOA5 gene 1131T/C sub-type Tip:coronary heart disease with diabetes mellitus group C allele carriers(CC+TC) TG and LP(a) levels were significantly higher than the C non-carriers (TT);CHD group and CHD with diabetes allele frequencies significantly higher in the control group.Diabetes group and the control group C was no significant difference in allele frequencies.Case Uighur groups,no difference between genotype frequencies of the Han,in coronary heart disease with diabetes mellitus group Uygur C allele frequency is higher than the Han in CHD group and diabetes group.2) APOB gene polymorphism and blood lipid target EocRI no obvious relevance,although one of A allele frequencies in theCHDgroup,diabetic control group,but did not reach statistical significance,patients with coronary heart disease in diabetic and control groups the same,A allele frequency and incidence of coronary heart disease there is no consistency,coronary heart disease allele frequency of group A the highest,followed by diabetic group,diabetic patients with coronary heart disease group and the control group;A allele with elevated blood lipids and crown heart disease unrelated to happen,cases and controls the distribution between the A allele frequency was no significant difference.Group A allele carriers of coronary heart disease with diabetes is higher than G allele carriers BMI;in coronary heart disease group and CHD with diabetes group Uygur GA genotype frequency and allele frequency is higher than the Han nationality,and in the group of diabetic there is no difference.3) D442G in the CETP gene among the four groups were found mutation D442G homozygote GG genotype,coronary heart disease group D442G mutation in CETP gene frequency of 4.5%(5/112),coronary heart disease with diabetes mutation rate of 3.9% (6/154),diabetes,mutation rate 4.9%(6/122),while the control group,3.7%mutation frequency(5/136),case and control groups were not statistically significant mutation frequency(P＞0.05).Two groups are consistent with Hardy- Weinberg balance,with a representative group.Conclusion:The high blood lipids,hypertension,high blood sugar, body mass index is higher in diabetic patients with coronary heart disease risk factors of coronary heart disease group similar group of diabetic hypertension,high blood lipids, body mass index increase in risk factors.4) diabetic group,coronary heart disease group, diabetic patients with coronary heart disease group TG,TC,LDL,APOB,blood sugar were higher,reaching statistical difference,P value＜0.05,Between the three age groups, BMI,HDL-C,LDL-C,APOA1,showed differences in smoking,one group of diabetic patients with coronary heart disease higher in the diabetic group and coronary heart disease group,but after no significant differences between the two groups.Coronary heart disease Uighur group HDL-C was significantly lower than the Han,in the diabetic group, no significant differences in the target.,Diabetic patients with coronary heart disease is lower than the mean age group of Uygur Han,BMI is higher than the Han.Uygurs in the control group BMI,,FBG,TG,APOB/A is higher than the Han.5) age,BMI,TG,LDL-C, LP-a is an independent risk factor for coronary heart disease,women are protective factors,LDL-C is one of the most prominent risk factors.Age,BMI,TC,LDL-C,LP-a coronary heart disease and diabetes are independent risk factors,women,HDL-C are protective factors.Age,TC,TG are an independent risk factor for diabetes.Conclusion: APOA5 allele C may be associated with increased TG and LP-a related,C allele are probably Uygur diabetes susceptibility gene with coronary heart disease;APOB gene A allele EocRI gene target with no obvious relationship between blood lipid,Uygur A allele and diabetic patients with coronary heart disease and coronary heart disease may be related;A alleles are possible coronary heart disease and diabetic with coronary heart disease susceptibility gene Uygur;CETP gene D442G in G and serum lipids and diabetes mellitus with coronary heart disease and coronary heart disease,diabetes probably does not matter.High blood cholesterol,high blood pressure,high blood sugar,body mass index increase in diabetes mellitus are risk factors for coronary heart disease and risk factors for coronary heart disease,hypertension,hyperlipidemia,increased body mass index are risk factors for diabetes.Uygur Han has more obvious than the lipid metabolism disorders,diabetes mellitus with coronary heart disease in younger age at onset Uygur.更多还原