Study On Relationship Between A-20C Angiotensinogen Gene Polymorphisms And Diabetic Nephropathy Of Type 2 Diabetic Patients

Objective:To investigate the relationship between A-20C angiotensinogen gene polymorphism and the susceptibility to type 2 diabetic nephropathy. If one susceptible gene of type 2 diabetic nephropathy is determined, our research can provide reliable theory to select people in the high-risk group of developing type 2 diabetic nephropathy. So they can be treated earlier for preventions.Methods:Our research chose 157 healthy volunteers(normal control group, NC) and 226 people with type 2 diabetes(T2DM) randomly in Chinese Han population from Zhejiang Province, and then divided the group of T2DM into two subgroups according to the value of microalbumin/creatinine (MALB/CR). Use MDRD formula to calculate estimated Glomerular Filtration Rate(eGFR), then divided the diabetic nephropathy group into two subgroups according to the value of eGFR. Using Polymerase Chain Reaction- Restriction Fragment Length Polymorphism(PCR-RFLP) to detect A-20C angiotensinogen gene polymorphisms of each subject. We explored the distribution of three genotypes and the frequency of two alleles in each group, to analyze whether there were significant differences between them. Also our research measured the general clinic information, such as body mass index(BMI), blood pressure, fasting blood glucose(FPG), HbAlc and lipid profiles, serum creatinine (SCr), and so on, to analyze whether A-20C angiotensinogen gene polymorphisms had influence on them. Binary Logistic Regressioin was also used to analyze the relationship between different groups.Results:1. The angiotensinogen gene A-20C polymorphism was screened in NC group and T2DM group, AA,AC and CC genotype and A, C allele were found. The genotype distribution in each group was in the Hardy—Weinberg equilibrium(P>0.05).2. The frequency of the genotype and allele in NC group was 72.0% for AA, 24.2% for AC,3.8% for CC genotype,84.1% for A allele. There was no significant difference for the frequency of the genotypes (P=0.613) and alleles (P=0.233) in the NC group between male and female subjects.3. For male subjects, the frequency of genotype and allele had no significant difference among the groups of NC,T2DM with diabetic nephropathy and T2DM without diabetic nephropathy. No significant difference was found among these three groups among female subjects, either.4. The frequency of genotype and allele between microalbuminuria group and macroalbuminuria group had no significant differences(P>0.05) in each sex. No significant difference was found between the groups with and without renal failure, either. 5. No significant differences were found in duration of disease, BMI, waistline, SBP, DBP, FPG,2-hour postprandial blood glucose, fasting insulin level,2-hour postprandial insulin level,TC,TG,HDL-c,LDL-c,HbAlc,SCr,MA and eGFR between the groups with and without C mutation.6. Binary logistic regressioin analysis indicated that waistline and SBP level were independent risk factors for diabetic nephropathy, and the duration of disease was an independent risk factor for proteinuria.Conclusion:1.There was a polymorphism of A-20C angiotensinogen gene in Zhejang Han population. The distribution of there genotypes and the frequency of two alleles didn't have significant differences between male and female healthy subjects.2. Angiotensinogen gene A-20C polymorphism might not be a susceptibility gene for type 2 diabetes, and also it might not be associated with diabetic nephropathy and the decline of renal function in type 2 diabetes patients in Zhejiang Han population.3. Angiotensinogen gene A-20C polymorphism might not be associated with duration of disease,BMI,waistline,SBP,DBP,FPG,2-hour postprandial blood glucose,fasting insulin level,2-hour postprandial insulin level,TC,TG,HDL-c,LDL-c,HbAlc,SCr,MA and eGFR.4. Waistline and SBP level were independent risk factors for diabetic nephropathy, and the duration of disease was an independent risk factor for proteinuria.