Preliminary Study On The Catalase Gene Polymorphism And Function

Catalase is an important antioxidant enzyme and is chosen as a candidate gene for essential hypertension and other cardiovascular diseases by its physiological role of antioxidation. We have identified a SNP-the catalase gene SNP-844C/T, which is strongly associated with essential hypertension after the study of isolated population of Dabie Mountain in Anhui province. Considering the genetic homogeneity of isolated population, we further carried on the case-control studies among the outbred population composed of 926 individuals from shanghai area (affected,448 subjects; control,478 subjects) .The results confirmed the association between genotype, allele frequencies and phenotype. The association is more evident after age stratification. The above data proved that it is effective to analyze hypertension associated genes in isolated population.We further studied the influence of variation of SNP-844 C/T on catalase expression and blood. The expression of reporter gene luciferase is analyzed in several cell lines transfected with construct vectors containing 1.14Kb catalase upstream sequence with either C or T variant .It is observed that the expression of luciferase increase by 22% with C variant than T variant in HepG2, while the expressions of luciferase increased by 47.5%, 132% and 56.58% separately transfected with T variant compared with C variant in ECV-304, 293 ,and HeLa cell lines. HepG2 is AP-2 deficient and AP-2 protein is expressed in other three cell lines. The results of gel shift and supershift assays showed that C variant could bind AP-2 protein strongly while the T variant demonstrated poorly as the binding activity is concerned. The results of western blot demonstrated an increase trend of catalase protein from T/T, T/C to C/C genotypes in blood .From above data, AP-2 is postulated to be a repressor of catalase. And other transcription factors as potential enhancer is predicted to exist in blood while not in endothelial. The normal function of endothelial is related to the ability of disposal of oxidants by blood microenviroment. And catalase can dispose H₂O₂ released from vascular endothelial which is important in the balance of redox metabolism in endothelial cell. We propose that the redox metabolism of endothelial is balanced under C/C genotype. However the...