Study On The Relationship Between NPHS2 Gene Polymorphism And Type 2 Diabetic Nephropathy

Objective:To investigate the relationship between NPHS2 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 NPHS2 gene polymorphism (G755→A) were determined by polymerase chain reaction- restriction fragment-length polymorphism analysis (PCR-RFLP) in 84 normal controls (NC) subjects and 141 type 2 diabetic patients(T2DM) in Chinese Han population in Zhejiang region. Type 2 diabetic patients were divided into two groups defined by the uriary albumin excretion rate(UAER) which consisted of diabetic nephropathy(DN+) group(67 patients) and non-diabetic nephropathy (DN-) group(74 patients). General clinic information ,such as body mass index (BMI), blood pressure ,fasting blood glucose (FPG) ,HbA₁c and lipid profiles were measured.Results:1 . NPHS2 gene include 3 genotypes ( GG, GA, AA) and 2 allele genes ( G or A).2, There was not statically significant difference of genotypes frequency [GG,GA, AA=47.6%, 41.7%, 10.7% (NC group) VS. 39.0%,45.4%,15.6% (DM group ), x² =2.004, P=0.367] and allele frequency [G, A = 68.5%, 31.5%(NC group)VS. 61.7%, 38.3% (DM group), x² =2.088, P=0.148]of G775→A polymorphism in NPHS2 gene between type 2 diabetes and normal control subjects.3,The AA genotype frequency in DN(+) group( 19.4%)has no statically significant difference with DN(-) group(12.2% ) and NC group(10.7%), (x²=7.963 and 7.264, P =0.019 and 0.026 >a =0.017);The A allele frequency in DN(+) group was 46.3%, which was significantly higher than DN(-) group(31.1%) and NC group (31.5%) (X²=0.263 and 0.008, P=0.009 and 0.0092=6.906, P =0.009);The A allele frequency in DN(macro) group was 61.8%, which was significantly higher than DN(micro) group(41.0%) (x2=4.401, P=0.036).5, Multiple logistic regression analysis of the risk factors revealed that the A allele of NPHS2 gene act as the independent risk factors for type 2 diabetic patients with massive proteinuria, OR= 15.756 (95% CI: 1.515-163.805,p<0.05) .Conclusion:1, NPHS2 gene include 3 genotype (GG, GA, AA) and 2 allele gene ( G or A) in Chinese people in Zhejiang region.2, There weren't statically significant difference of genotypes frequency and allele frequency of G755→A polymorphism in NPHS2 gene between T2DM group and NC group. There was not enough association of the polymorphism with type 2 diabetes mellitus.3^ The A allele frequency in diabetic nephropathy was significant difference between normal controls and type 2 diabetic patients without nephropathy;The AA genotype frequency and A allele frequency in DN(macro) group was significant difference with those in DN(micro) group.4n The A allele of NPHS2 gene acts as the independent risk factors for type 2 diabetic patients with massive proteinuria. NPHS2 gene G755—-A mutation may one of the genetic susceptible factors for type 2 diabetes with massive proteinuria.