Polymorphism In The Apoliprotein A5 Gene And Their Association With Coronary Heart Disease In Chinese

PROJECT :Investigate the three known polymorphisms of APOA5 gene (-1131T>C,-12,238T>C, S19W— SNP3,4,5)and the association of this gene with CHD in Chinese Han population of 286 CHD patients and 395 healthy persons.METHOD:Polymerase chain reaction/restriction fragment length polymorphism(PCR-RFLP ), and other methods.RESULTS : 1 Allelic frequencies of MseI restriction polymorphism in the promoter of APOA5 gene were 0.223,0.777 for allele T and C respectively,where T/C respresants allele with/without fragment of 154bp after MseI digestion of PCR products.These frequencies were significantly different from those reported in Japanese(0.223 vs 0.34,0.777 vs 0.66,P<0.05) and were much higher than European Caucasians(0.223 vs 0.06,0.777 vs 0.77,P<0.05).There were significantly differences in frequencies of the alleles and genotypes in MseI polymorphisms between CHD and control groups(P<0.05).In patients group,the levels of triglycererid (TG) and cholesterol (CHOL) with CC,TC genotypes were significantly higher than those with TT genotype.It means that genotypes having rare allele C were closely associated with the higher levels of plasma TG and CHOL (P<0.05).2 Allelic frequencies of HaeIII restriction polymorphism in the APOA4/A5 intergenic region of APOA5 gene were 0.626,0.374 for allele T and C respectively,where T/C respresants allele with/without fragment of 162bp after HaeIII digestion of PCR products.These frequencies were significantly different from those reported in European Caucasians (0.626vs 0.34,0.374 vs 0.66,P<0,001).There were significant differences in frequencies of the alleles and genotypes in HaeIII polymorphism between CHD and control groups (P>0.05).Morever,the levels of high density lipoprotein (HDL) in patients with CC genotype were significantly higher than those with TT and TC genotypes,which suggested that CC genotype were closely associated with the higher levels of HDL (P<0.01).3 Allelic frequencies of TaqI restriction polymorphism in the extron 2 of APOA5 gene were 0 and 1 for allele W and S respectively,where W/S respresants allele with/without fragment of 157bp after TaqI digestion of PCR products.These frequencies were significantly different from those reported in European Caucasians (0 vs 0.057,1 vs 0.943,P<0.05).There was significant difference in genotypes and in frequencies of the alleles in TaqI polymorphism between CHD and control groups. Hwever,there were no significant differences in the levels of various plasmid lipids (TG,CHOL,HDL-C,LDL-C) between SS and SW genetypes(P>0.05).CONCLUSION : Frequencies of the alleles and genotypes of -1131T>C position in the promoter of APOA5 gene were significantly different between the CHD group and the healthy group.Allele C was associated with the higher levels of plasma TG and CHOL.Frequencies of the alleles and genotypes in the APOA4/A5 intergenic region of APOA5 gene were significantly different between the CHD group and the healthy group.Morever,CC genetype was associated with the higher levels of plasma CHOL.Frequencies of genotypes in the extron 2 of APOA5 gene were significantly different between the CHD group and the healthy group. Therefore,it will be concluded that these three SNPs of APOA5 gene may relate to the plasma lipoproteins metabolism which is recognized as the risk factor of cardiocuscular disease in Chinese Han population.Because -1131T>C position and -12,238T>C position are in the uncoding region of APOA5 gene,they can not directly affect the expression of the protein.They may be in linkage disequilibrisum with other functional sites. More studies will be needed to find out the fact. S19W position lies in the extron 2 of APOA5 gene and changes the type of amino acid ,which can directly influence the expression of APOAV protein.But it has been unavailable about its concret function.