A Case-control Study On The Associations Of Polymorphisms Of AGT Gene And MTHFR Gene And Other Factors With The Risk Of Diabetic Nephropathy In Type 2 Diabetic Patients

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.