【作者】 李咏梅；

【导师】 齐秀英； 陈莉明；

【作者基本信息】 天津医科大学 ， 流行病学与卫生统计学， 2004， 硕士

【摘要】 目的：探讨ACE基因第16内含子的Alu序列插入／缺失(I／D)多态性及其它因素与2型糖尿病肾病(DN)的关系。 方法：采用以医院为基础的配对病例对照研究方法，对101对研究对象进行了研究。病例为2001年11月至2003年1月在天津医科大学代谢病医院住院的2型糖尿病肾病患者，对照为同期、在该医院住院的未合并肾病的2型糖尿病(DM)患者，配比条件为年龄和性别。对病例和对照使用统一的调查表进行调查，内容包括：人口统计学特征、疾病史、疾病家族史、饮食习惯、行为方式、社会心理因素以及体格检查和实验室检查等资料。应用聚合酶链反应(PCR)及琼脂糖凝胶电泳方法进行ACE基因多态性分析。采用条件logistic回归模型对DN的危险因素进行单因素和多因素分析。 结果：单因素条件logistic回归分析结果表明：ACE基因第16内含子的Alu序列插入／缺失(I／D)多态性与DN的发生之间有统计学关联，D等位基因的出现使DN发生的相对危险增加，与Ⅱ基因型相比，基因型为ID、DD的DM患者并发DN的OR值及其95％可信区间分别为2.419(95％CI：1.180～4.959)和3.417(95％CI：1.608～7.260)；经DM家族史、高血压史调整后，其统计学显著性仍然存在。单因素分析结果表明：文化程度、DM病程、血糖控制程度、DM家族史、既往高血压史、既往高血压治疗情况、豆类摄入、血清肌酐水平和血清高密度脂蛋白胆固醇水平与DN的发生有统计学关联，OR值及其95％可信区间分别为0.400(95％CI：0.176～0.908)、1.907(95％CI：1.399～2.601)、1.553(95％CI：1.033～2.337)、2.000(95％CI：1.097～3.644)、天津瞥澎比笋颐毖笋世艘丈2 .055(95%Cl:1.170~3.610)、1.540(1.123一2.111)、1.359(95%Cl是1 .010~1.828)、4.000(95%Cl:1.927~8.304)和0.390(95%Cl:0.164~0.924)。但是，经调整可能的混杂因素的作用后，文化程度、血糖控制情况、既往高血压治疗情况、高密度脂蛋白胆固醇水平等与DN发生之间的关系失去统计学意义。未发现高血压家族史、冠心病家族史、体育锻炼情况、吸烟、饮酒、饮茶、肉类摄入、蛋类摄入、奶类摄入、油脂摄入、蔬菜摄入、甜食摄入、怀孕次数、生产巨大儿史、性格特点、工作和生活中的不良应激事件、重大不幸生活事件、曾患有其他重大疾病或意外创伤、调查时体质指数以及血清总胆固醇、甘油三酷、低密度脂蛋白胆固醇和极低密度脂蛋白胆固醇水平与DN的发生之间有统计学关联。ACE基因型与DM病程之间的交互作用与DN发生之间的关联有统计学意义(OR=1 .741，95%cI:1.107~2.740)，ACE基因D等位基因和DM病程长同时存在的情况下，DN发生的危险性更大。多因素条件logistie回归分析结果显示，ACE基因型(OR二1.890，95%Cl:1.146一3.118)、DM病程(OR=2.302，95%Cl:1.507~3.515)、豆类摄入(OR二1.629，95%Cl:1.054~2.519)和血清肌配水平(OR=5.918，95忧I:2.224~15.750)为DN的独立危险因素。未发现ACE基因I/D多态性与DN病情轻重(DN分期)之间有统计学关联。 结论:ACE基因的D等位基因为DN的独立预报因子，DM病程长、豆类摄入多和血清肌醉水平高均可增加DN发生的危险性。更多还原

【Abstract】 Objectives: The aim of this study was to explore the associations between insertion/deletion (I/D) polymorphism of Alu sequence at intron 16 of the polymorphism of angiotensin-converting enzyme (ACE) gene and other factors and diabetic nephropathy(DN) in type 2 diabetic patients.Methods: A hospital-based case-control study was conducted in Tianjin from November 2001 to January 2003. 101 pairs of subjects were recruited. The cases were considered to be DN patients and the controls were considered to be type 2 diabetic patients (DM) without diabetic nephropathy. Each case was matched with one control on sex and age. Information was collected through face-to-face interview, which included demographic data, disease history, disease family history, dietetic habit, behavior pattern, social psychologic character, clinical data and laboratory data. I/D polymorphism of ACE gene was assessed by polymerase chain reaction (PCR) and the PCR products were subjected to electrophoresis on agarose gel that was stained with ethidium bromide. Using the conditional logistic regression model, we examined the effect of the collected factors on the risk of the diabetic nephropathy development. Results: Results from univariate conditional logistic regression analysis showedthat the I/D polymorphism of ACE gene was associated with development of diabetic nephropathy. D allele was more frequency among DN patients. Compared with the group of II genotype, the corresponding OR with 95% CI of the groups of ID genotype and DD genotype were 2.419( 1.180~4.959)and 3.417 (1.608~7.260) respectively. After adjusting for diabetic family history and history of hypertension, the results still showed that the association between ACE genotype and DN was statistically significant. Results from univariate conditional logistic regression analysis also showed that DN was associated with education level, diabetes duration, glycemia control, diabetic family history, history of hypertension, hypertension treatment, legume intake, serum creatinine level and serum level of high density lipoprotein (HDL) cholesterol. The corresponding OR with 95% CI were 0.400(0.176-0.908), 1.907(1.399-2.601), 1.553(1.033-2.337), 2.000(1.097-3.644), 2.055(1.170-3.610), 1.540(1.123-2.111), 1.359 (1.010-1.828), 4.000(1.927-8.304) and 0.390(0.164-0.924) respectively. However, after adjusting for possible confounding factors, the associations between these factors, including education level, glycemia control, hypertension treatment and serum HDL cholesterol level, and DN were statistically significant. No associations were observed between the following factors and DN, which were family history of hypertension, family history of coronary heart disease, exercise, smoking, alcohol drinking, tea drinking, meat intake, egg intake, milk intake, fat intake, vegetable intake, sweetmeat intake, times of pregnancy, the history of delivering macrosomia, character, body index, serum total cholesterol, triglycerides, low density lipoprotein and very low density lipoprotein cholesterol levels. ACE genotype and diabetes duration were found to have an interaction(OR=1.741, 95%CI:1.107 -2.740). When subjected to multivariate conditional logistic regression analysis, four factors remained statisticalassociations with DN, which were ACE genotype(OR=1.890, 95%CI:1.146~ 3.118), diabetes duration(OR=2.302, 95%CI:1.507 ~ 3.515), legume intake (OR=1.629, 95%CI:1.054~ 2.519) and serum creatinine level (OR=5.918, 95%CI:2.224~ 15.750). No association was observed between I/D polymorphism of ACE gene and DN stage.Conclusion: D allele of ACE gene was an independent predictive factor for diabetic nephropathy, long diabetes duration, increased legume intake and high serum creatinine level were associated with higher risk for the development of diabetic nephropathy.更多还原