A Study Of The Association Of The Tumor Necrosis Factor Gene Polymorphisms With The Susceptibility Of Dilated Cardiomyopathy

Background:The etiopathogenisis of dilated cardiomyopathy(DCM) is still uncertainnow, but the roles of genetic and the environmental factors are popularaccepted.With the study of more and more DCM families, the genetic factorhas become the focus. Tumor necrosis factor (TNF) genes are closely linkedto HLA genes and lie in the region of MHCⅢ. TNF gene polymorphismshave been found recently, which is associated with high TNF production,suggesting the involvement of a genetic predisposition to high TNFalpha(TNF-α) secretion in the development of DCM. Several studies haveshown that individual possible explanation for differential TNF-αproductioncould be the involvement of a polymorphism within the TNF gene. Ourobjective is to investigate the association of TNF gene polymorphisms andthe susceptibility of DCM.Object:To determine whether the polymorphisms within the TNF-αand TNFbeta(TNF-β) gene are associated with the susceptibility to Dilated Cardiomyopathy. To explore a useful gene marker to diagnoize DCMor prevent beforehand.Methods:(1) A case-control research was done on 110 DCM patients and 110healthy individuals as a control group. (2) DNA was extracted fromperipheral blood leukocytes. The special primers were designed according tothe public gene information. (3)The gene polymorphisms of TNF-αandTNF-βwere detected and analyzed by polymerase chain reaction (PCR) andrestriction fragment length polymorphisms (RFLP) techniques. (4) Statisticalevaluation was carried out with SPSS 13.0 statistical analysis software.Genotypes distribution underwent the Hardy-Weinberg-Equilibrium(HWE)calculation, and the control group is representative of the overall population.Results:The frequency of A allele of TNF-α(-308) locus in DCM patients weresignificantly higher than that in health control group (p＜0.05). Thefrequencies of the AA genotype and the A allele of TNF-β(+252) locuswere 31％and 48.6％respectively in DCM patients which are significantlyincreased compared with the healthy control, The P values are 0.038 and0.003 respectively by analyzing the dates with SPSS13.0. There were nosignificantly differences in the distribution of the genotypic polymorphismsof the TNF-α(-857),TNF-α(-863),TNF-α(-1031) loci between the DCMgroup and the health control.Conclusions:(1)The study reveals that the A allele of TNF-α(-308) and TNF-β(+252) loci are positively correlated with DCM, and confirms the role of inheritancein DCM.(2)The AA genotype of TNF-β(+252) detected in this study might be asusceptible factor in the pathogenesis of DCM, and individuals with TNF-β(+252) AA genotype are susceptible to DCM.(3)People who carries A allele in TNF gene loci have a large tendency tosuffer DCM.(4)The results of our study show that the promoter polymorphisms ofTNF-α(-857),TNF-α(-863),TNF-α(-1031) are similar in both DCMpatients and the healthy control. It means that TNF gene polymorphisms arenot associated with the susceptibility to DCM.