AGT基因和MTHFR基因多态性及其它因素与糖尿病肾病关系的病例对照研究
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摘要
目的：探讨AGT基因和MTHFR基因多态性及其它因素与糖尿病肾病的关系,为预防2型糖尿病患者发生肾功能损害以及防止向终末期肾病发展提供科学依据。
方法：采用以医院为基础的成组病例对照研究方法,对126例2型糖尿病并发肾病患者(病例组)和212例未并发肾病的2型糖尿病患者(对照组)进行研究。病例和对照均来自2009年6月至2010年1月期间在天津医科大学代谢病医院住院的2型糖尿病患者。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、社会心理因素等资料,并进行体格检查和实验室检查。应用聚合酶链式反应-限制性片断长度多态性(PCR-RFLP)技术进行AGT基因和MTHFR基因多态性分析。采用单因素和多因素非条件Logistic回归模型分析2型糖尿病肾病相关因素的比值比(OR)及其95%可信区间(95%CI)。
结果：
1.单因素Logistic回归分析结果显示AGT基因M235T多态性与2型糖尿病肾病之间存在统计学关联,携带AGT T等位基因的2型糖尿病患者发生DN的危险性高于M等位基因携带者,OR值及其95%CI为2.471(1.483～4.115),且经过DM家族史、DM病程和MTHFR等位基因调整后二者间的统计学关联仍然存在。
2.单因素Logistic回归分析结果显示MTHFR基因C677T多态性与2型糖尿病肾病之间也存在统计学关联,携带MTHFR T等位基因的2型糖尿病患者发生DN的危险性是C等位基因携带者的1.670倍,经过DM家族史和DM病程调整后二者间的统计学关联仍然存在,但经AGT等位基因调整后,MTHFR等位基因与DN之间的统计学关联消失。
3.单因素Logistic回归分析结果表明：糖尿病病程、并发视网膜病变、并发冠心病、既往高血压史、既往高血压控制情况、嗜咸饮食、体质指数(BMI)、调查时测得的收缩压及血清总胆固醇(TC)水平与DN之间有统计学关联,其OR及95%CI分别为：1.528(1.251～1.865)、2.763(1.753～4.355)、2.524(1.513～4.211)、1.863(1.151～3.016)、2.789(1.351～5.759)、1.618(1.024～2.555)、1.456(1.064～1.992)、2.183(1.388～3.433)和1.597(1.044～2.444)。经过调整可能的混杂因素的作用后,TC水平与DN的关联性消失。
4.未发现年龄、性别、文化程度、脑力劳动、婚姻状况、空腹血糖、餐后2小时血糖、酮症、血糖控制情况、糖尿病的治疗方式、高脂血症史、糖尿病家族史、高血压家族史、冠心病家族史、吸烟、饮酒、体育锻炼、蛋类摄入、奶类摄入、蔬菜摄入、嗜甜饮食、性格、调查时血清甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、极低密度脂蛋白胆固醇、纤维蛋白原水平及腰臀比(WHR)等因素与DN的发生之间存在统计学关联。
5.将所有单因素Logistic回归分析有意义的变量,应用前进法进行多因素非条件Logistic回归分析拟合主效应模型,共有4个因素进入主效应方程,依次为：AGT基因型、糖尿病并发视网膜病变、高血压史和糖尿病病程,其OR值和95%CI分别为2.537(1.445～4.454)、2.286(1.180～4.428)、2.456(1.158～5.206)和1.354(1.007～1.821)。
结论：AGT基因235T等位基因、糖尿病病程长、既往高血压史均可增加2型糖尿病患者合并肾病的危险；糖尿病并发视网膜病变与2型糖尿病肾病之间有统计学关联。
Objective:The aim of the study is to explore the associations of polymorphisms of angiotensinogen (AGT) gene and methylenete-trahydrofolate reductase (MTHFR) gene and other factors with the risk of diabetic nephropathy in type 2 diabetic patients and to provide scientific basis for the prevention of renal dysfunction and the development of end stage renal disease in patients with type 2 diabetes mellitus.
Methods:A hospital-based case-control study was conducted in Tianjin from June 2009 to January 2010.126 cases with type 2 diabetic nephropathy and 212 controls of type 2 diabetic patients without nephropathy were recruited. 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. Polymorphisms of AGT gene M235T and MTHFR gene C677T were assessed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Data were analyzed using univariate and multivariate non-conditional logistic regression to estimate odds ratio (OR) and 95% confidence interval (CI).
Results:
1. Results of univariate logistic regression analysis showed that AGT gene M235T polymorphism was associated statistically with the risk of nephropathy in type 2 diabetic patients. Type 2 diabetic patients with allele T of AGT gene M235T had a greater risk of nephropathy than those with allele M, the OR and 95% CI were 2.471 (1.483-4.115). After adjusting for family history of diabetes, diabetic duration and allele T of MTHFR gene C677T, the results still showed that AGT gene polymorphism was associated statistically with the risk of nephropathy in type 2 diabetic patients.
2. Results of univariate logistic regression analysis showed that MTHFR gene C677T polymorphism was associated with the risk of nephropathy in type 2 diabetic patients. Type 2 diabetic patients with allele T of MTHFR gene C677T had higher risk of nephropathy than those with allele C, the OR and 95%CI were 1.670 (1.106-2.521), and the association was still significant after adjusting for family history of diabetes and diabetic duration. But the results showed that MTHFR gene C677T polymorphism was not associated statistically with the risk of nephropathy in type 2 diabetic patients after adjusting for allele T of of AGT gene M235T.
3. The results of univariate logistic regression analysis also showed that the risk of nephropathy in type 2 diabetic patients was associated with diabetes duration, diabetic retinopathy, diabetes complicated by coronary artery disease, history of hypertension, hypertension control, salt intake, body mass index (BMI), systolic blood pressure and serum total cholesterol level at investigation. The corresponding ORs with 95% CIs were 1.528 (1.251-1.865),2.763 (1.753-4.355),2.524 (1.513-4.211),1.863 (1.151-3.016), 2.789(1.351-5.759),1.618(1.024-2.555),1.456(1.064-1.992),2.183(1.388-3.433) and 1.597 (1.044-2.444) respectively. However, after adjusting for possible confounding factors, the association between the risk of diabetic nephropathy and serum total cholesterol level at investigation was not statistically significant.
4. No associations were observed between the following factors and the risk of diabetic nephropathy, such as age, gender, education level, intellectual work, marital condition, fasting plasm glucose, postprandial plasm glucose, ketosis, plasm glucose control, types of treatment for diabetes, the history of hyperlipidemia, family histories of diabetes, hypertension and coronary heart disease, smoking, alcohol drinking, physical exercise, egg intake, milk intake, vegetable intake, sweetmeat intake, character, serum triglycerides, high density lipoprotein cholesterol levels, low density lipoprotein cholesterol levels, very low density lipoprotein cholesterol levels, plasma fibrinogen levels and waist-to-hip ratio (WHR) at investigation.
5. Four factors related to the risk of diabetic nephropathy were introducted into multivariate non-conditional logistic regression equation, which included AGT gene M235T polymorphism, diabetic retinopathy, history of hypertension and diabetes duration. The ORs and 95%CIs were 2.537 (1.445-4.454),2.286 (1.180-4.428),2.456 (1.158-5.206) and 1.354 (1.007-1.821) respectively.
Conclusion:Allele T of AGT gene M235T, the longer diabetes duration and history of hypertension were associated with higher risk of nephropathy in type 2 diabetic patients. In addition, diabetic retinopathy was associated with higher risk of diabetic nephropathyr.
方法：采用以医院为基础的成组病例对照研究方法,对126例2型糖尿病并发肾病患者(病例组)和212例未并发肾病的2型糖尿病患者(对照组)进行研究。病例和对照均来自2009年6月至2010年1月期间在天津医科大学代谢病医院住院的2型糖尿病患者。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、社会心理因素等资料,并进行体格检查和实验室检查。应用聚合酶链式反应-限制性片断长度多态性(PCR-RFLP)技术进行AGT基因和MTHFR基因多态性分析。采用单因素和多因素非条件Logistic回归模型分析2型糖尿病肾病相关因素的比值比(OR)及其95%可信区间(95%CI)。
结果：
1.单因素Logistic回归分析结果显示AGT基因M235T多态性与2型糖尿病肾病之间存在统计学关联,携带AGT T等位基因的2型糖尿病患者发生DN的危险性高于M等位基因携带者,OR值及其95%CI为2.471(1.483～4.115),且经过DM家族史、DM病程和MTHFR等位基因调整后二者间的统计学关联仍然存在。
2.单因素Logistic回归分析结果显示MTHFR基因C677T多态性与2型糖尿病肾病之间也存在统计学关联,携带MTHFR T等位基因的2型糖尿病患者发生DN的危险性是C等位基因携带者的1.670倍,经过DM家族史和DM病程调整后二者间的统计学关联仍然存在,但经AGT等位基因调整后,MTHFR等位基因与DN之间的统计学关联消失。
3.单因素Logistic回归分析结果表明：糖尿病病程、并发视网膜病变、并发冠心病、既往高血压史、既往高血压控制情况、嗜咸饮食、体质指数(BMI)、调查时测得的收缩压及血清总胆固醇(TC)水平与DN之间有统计学关联,其OR及95%CI分别为：1.528(1.251～1.865)、2.763(1.753～4.355)、2.524(1.513～4.211)、1.863(1.151～3.016)、2.789(1.351～5.759)、1.618(1.024～2.555)、1.456(1.064～1.992)、2.183(1.388～3.433)和1.597(1.044～2.444)。经过调整可能的混杂因素的作用后,TC水平与DN的关联性消失。
4.未发现年龄、性别、文化程度、脑力劳动、婚姻状况、空腹血糖、餐后2小时血糖、酮症、血糖控制情况、糖尿病的治疗方式、高脂血症史、糖尿病家族史、高血压家族史、冠心病家族史、吸烟、饮酒、体育锻炼、蛋类摄入、奶类摄入、蔬菜摄入、嗜甜饮食、性格、调查时血清甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、极低密度脂蛋白胆固醇、纤维蛋白原水平及腰臀比(WHR)等因素与DN的发生之间存在统计学关联。
5.将所有单因素Logistic回归分析有意义的变量,应用前进法进行多因素非条件Logistic回归分析拟合主效应模型,共有4个因素进入主效应方程,依次为：AGT基因型、糖尿病并发视网膜病变、高血压史和糖尿病病程,其OR值和95%CI分别为2.537(1.445～4.454)、2.286(1.180～4.428)、2.456(1.158～5.206)和1.354(1.007～1.821)。
结论：AGT基因235T等位基因、糖尿病病程长、既往高血压史均可增加2型糖尿病患者合并肾病的危险；糖尿病并发视网膜病变与2型糖尿病肾病之间有统计学关联。
Objective:The aim of the study is to explore the associations of polymorphisms of angiotensinogen (AGT) gene and methylenete-trahydrofolate reductase (MTHFR) gene and other factors with the risk of diabetic nephropathy in type 2 diabetic patients and to provide scientific basis for the prevention of renal dysfunction and the development of end stage renal disease in patients with type 2 diabetes mellitus.
Methods:A hospital-based case-control study was conducted in Tianjin from June 2009 to January 2010.126 cases with type 2 diabetic nephropathy and 212 controls of type 2 diabetic patients without nephropathy were recruited. 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. Polymorphisms of AGT gene M235T and MTHFR gene C677T were assessed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Data were analyzed using univariate and multivariate non-conditional logistic regression to estimate odds ratio (OR) and 95% confidence interval (CI).
Results:
1. Results of univariate logistic regression analysis showed that AGT gene M235T polymorphism was associated statistically with the risk of nephropathy in type 2 diabetic patients. Type 2 diabetic patients with allele T of AGT gene M235T had a greater risk of nephropathy than those with allele M, the OR and 95% CI were 2.471 (1.483-4.115). After adjusting for family history of diabetes, diabetic duration and allele T of MTHFR gene C677T, the results still showed that AGT gene polymorphism was associated statistically with the risk of nephropathy in type 2 diabetic patients.
2. Results of univariate logistic regression analysis showed that MTHFR gene C677T polymorphism was associated with the risk of nephropathy in type 2 diabetic patients. Type 2 diabetic patients with allele T of MTHFR gene C677T had higher risk of nephropathy than those with allele C, the OR and 95%CI were 1.670 (1.106-2.521), and the association was still significant after adjusting for family history of diabetes and diabetic duration. But the results showed that MTHFR gene C677T polymorphism was not associated statistically with the risk of nephropathy in type 2 diabetic patients after adjusting for allele T of of AGT gene M235T.
3. The results of univariate logistic regression analysis also showed that the risk of nephropathy in type 2 diabetic patients was associated with diabetes duration, diabetic retinopathy, diabetes complicated by coronary artery disease, history of hypertension, hypertension control, salt intake, body mass index (BMI), systolic blood pressure and serum total cholesterol level at investigation. The corresponding ORs with 95% CIs were 1.528 (1.251-1.865),2.763 (1.753-4.355),2.524 (1.513-4.211),1.863 (1.151-3.016), 2.789(1.351-5.759),1.618(1.024-2.555),1.456(1.064-1.992),2.183(1.388-3.433) and 1.597 (1.044-2.444) respectively. However, after adjusting for possible confounding factors, the association between the risk of diabetic nephropathy and serum total cholesterol level at investigation was not statistically significant.
4. No associations were observed between the following factors and the risk of diabetic nephropathy, such as age, gender, education level, intellectual work, marital condition, fasting plasm glucose, postprandial plasm glucose, ketosis, plasm glucose control, types of treatment for diabetes, the history of hyperlipidemia, family histories of diabetes, hypertension and coronary heart disease, smoking, alcohol drinking, physical exercise, egg intake, milk intake, vegetable intake, sweetmeat intake, character, serum triglycerides, high density lipoprotein cholesterol levels, low density lipoprotein cholesterol levels, very low density lipoprotein cholesterol levels, plasma fibrinogen levels and waist-to-hip ratio (WHR) at investigation.
5. Four factors related to the risk of diabetic nephropathy were introducted into multivariate non-conditional logistic regression equation, which included AGT gene M235T polymorphism, diabetic retinopathy, history of hypertension and diabetes duration. The ORs and 95%CIs were 2.537 (1.445-4.454),2.286 (1.180-4.428),2.456 (1.158-5.206) and 1.354 (1.007-1.821) respectively.
Conclusion:Allele T of AGT gene M235T, the longer diabetes duration and history of hypertension were associated with higher risk of nephropathy in type 2 diabetic patients. In addition, diabetic retinopathy was associated with higher risk of diabetic nephropathyr.
引文
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