Association Of A T29→C Polymorphism Of The TGF-β₁ Gene With Genetic Susceptibility To Type 2 Diabetic Nephropathy

Objective: To investigate the relationship between transforming growth factor-beta1 (TGF-β1) gene polymorphism and the susceptibility to type 2 diabetic nephropathy. To ensure the susceptible gene of type 2 diabetic nephropathy (DN) , and illustrate the causes of diabetes from gene level and provide reliable theory to select the high crisis people of DN .In order to find and treat diabetes early ,prolong the time that patients live as well as promote the quality of life.Methods: The genotypes of TGF-β1 gene polymorphism (T29 →C) was determined by polymerase chain reaction-restriction fragment-length polymorphism analysis in 62 normal control(NC) subjects and 167 type 2 diabetic patients(T2DM) in Chinese people in FuJian region. Type 2 diabetic patients were divided into three groups defined by the urine albumin-to-creatinine ration (ACR) which consisted of including micro urine albumin(UA) group(44) ,macro urine albumin(MA) group(36) and non-diabetic nephropathy (DN-) group(87). The serum concentration of TGF-β1 was qualified by the ELISA assay . At the same time , to obtain general clinicinformation ,such as body mass index ( BMI ), blood pressure ,fasting blood glucose (FPG) and so on.Result: 1. TGF-β1 gene include 3 genotype ( CC,TC,TT ) and 2 allele gene ( C or T ). 2. There weren't statically significant difference of genotypes frequency [CC,CT,TT=30.6%,43.6%,25.8%(NC group) VS.42.5%,37.7%,19.8%(DM group ) X2 =2.783 P 〉0.05] and allele frequency [C,T=52.4%,47.6%(NC组)VS.61.4%,38.6% (DM 组),X2 =2.999 P 〉0.05]of T29→C polymorphism in TGF-β1 gene between type 2 diabetes and normal control subjects. 3. CC genotype frequency of DN(+) group(46.3%) is markedly higher than that of DN(-) group(39.1%) and NC group(30.6%), X2 =7.061,6.37, P < 0.05 ;C allele gene frequency of DN(+) group(67.5%) also higher than that of DN(-) group(55.7%) and NC group(52.4%),X2 =4.857,6.673 P < 0.05。There was no significantly difference between DN(-) group and NC group, X2 =1.772,0.323 P 〉0.05. 4. Multiple logistic regression analysis of the risk factors associated with diabetic nephropathy revealed that the C allele of TGF-β1 gene act as the independent risk factors for diabetic nephropathy , OR=0.244( 95%CI:0.064～0.924 P<0.05) 5. With the development of type 2 diabetic nephropathy ,the serum concentration of TGF-β1 increased. There were positive relationship between the serum concentration of TGF-β1 and lnACR (r=0.621, P < 0.05). Conclusion: 1. TGF-β1 gene include 3 genotype ( CC,TC,TT ) and 2 allele gene ( C or T ) in Chinese people in FuJian region.2. There weren't statically significant difference of genotypes frequency and allele frequency of T29→C polymorphism in TGF-β1 gene between T2DM group and NC group. There weren't enough association of the polymorphism with type 2 diabetes mellitus.3. The T29→C polymorphism of the TGF-β1 gene is significantly associated with type 2 diabetic nephropathy . TGF-β1 gene T29 →C mutation is one of the genetic susceptible factors for type 2 diabetes nephropathy ,mutate C allele gene is susceptible gene of DN.4. Serum concentration of TGF-beta1 was associated with the progression of diabetic nephropathy.5. To observe the serum TGF-beta1 and TGF-β1 gene polymorphism will contribute to find and treat diabetes early ,prolong the time that patients live as well as promote the quality of life.