Study On The Relationship Of Polymorphism Of PPAR-γ2 And Type 2 Diabetes And Diabetic Nephropathy

ObjectivePeroxisome proliferator-activated receptor gamma2(PPARr 2) is a member of the nuclear hormone receptor superfamily , it is a main regulator of adipose differentiation, and possibly associated with energy metabolism and insulin sensitivity. The Prol2Ala mutation is a common variants of PPAR r 2 existed in exon B. The frequency of the mutation is different among ethnic and population. Whether the polymorphism is associated with type 2 diabetes is controversial. In additional, some study observation suggested a protective effect of the Alal2 allele in relation to diabetic nephropathy. Most interesting is that thiazolidinediones(TZDs) act as PPARr ligands and have been reported to decrease albuminuria in patients with early diabetic nephropathy. The aim of our experiments is to investigate the relationship between the Prol2Ala polymorphism of PPARr2 and type 2 diabetes or diabetic nephropathy.MethodsAccording to the diagnostic criteria of ADA in 1997, weselected 329 subjects with type 2 diabetes and 103 non-diabetes subjects, the clinical data were collected. Genomic DNA was extracted from peripheral blood leucocytes of the participants. We screen the Prol2Ala polymorphism by means of PCR-RFLP in all subjects and identification the mutation by directly sequenced the PCR production. At last we compaired the difference offrequency in allele and genotype among groups. Results1. We screened 32 mutations from 328 diabetic subjects including 31 hetero-mutation and 1 homomutation. In the control group, there are 20 heter-mutations and non homo-mutation. The frequency of the Prol2Ala mutation was significantly lower in diabetic subjects than in non-diabetic subjects(0.098 vs 0.194).2 . But the frequency of mutation did not differ significantly among the diabetic nephropathy groups.3. In the control group, the TG, TC, VLDL, HDL, LDL, BP and BMI have no difference between CC genotype and GG genotype.4. In the diabetes group, the TG, TC, VLDL, HDL, LDL, BP, FPGand BMI have no difference among the genotypes.Conclusion1. Our study suggest that in Tianjin area the Alal2 allele is associated with a reduced risk for the development of diabetes in general population.2. From the non-diabetic nephropathy to early nephropathy and to clinical nephropathy, the frequency of Ala allele is increasing, but the different is no statistic significant, that is the variant is not associated with diabetic nephropathy.3. The Ala allele has no effect on TG, TC, VLDL, HDL, LDL, BP, FPG and BMI.