Heme Oxygenase-1,Tumor Necrosis Factor-α,Microsomal Epoxide Hydrolase Gene Polymorphism And Susceptibility To Chronic Obstructive Pulmonary Disease

Object Chronic Obstructive Pulmonary Disease (COPD) is a disease characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and results from an abnormal inflammatory response of the lungs to noxious particles and gases.It has been identified that COPD is the result of an environmental insult and the response of the host that is primarily genetically predetermined.However,the only established genetic risk factor of COPD is homozygousity of α₁-antitrypsin (α₁-AT) gene.Other genetic risk factors of COPD are uncertain. We investigated whether polymorphisms in gene for heme oxygenase-1, tumor necrosis factor- α, microsomal epoxide hydrolase have any relations on individual susceptibility to the development of chronic obstructive pulmonary disease in order to find out the "susceptible" gene for COPD in Han nationality of China.Through the gene-environment and gene-gene interaction analysis,we can selecet the high dangerous population to prevent earlier and reduce the incidence of COPD.Materials and Methods The research design was a case-control study.After we selected the peripheral blood of 64 COPD patients and 56 healthy controls in Han nationality,we extracted their genomic DNA.Polymerase chain reaction (PCR) wasperformed to detect HO-1 double nuceleotide (GT) repeat polymorphism,Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were performed to detect TNF-a -308(G/A)% mEH exon 3 (TyrllSHis^ mEH exon 4 (Hisl39Arg) single nucleotide polymorphism.We also selected the clinical and laboratorial items for the research.The data of age and lung function of this study were analyzed by test t test,the data of frequency of allele and genetype were analyzed by Chi square.The Logistic analysis were performed to investigate the relationship between risk factors and COPD.Rcsult 1 ^ The GT repeat number of HO-1 gene promoter is various from 15⁴0, allele frequencies of the long repeat sequence (repeat number exceeds 30, allele L) were significantly different between the groups:21.88% in COPD and 10.72% in control subjects^ The TNF- a -308 A allele frequencies were significantly different between the groups: 18.75% in COPD and 7.14%in control subjects^ The frequency of polymorphic genetypes of mEH exon3 showed no difference between the COPD group and the control group:mEH exon3 homozygous wild-type-. heterozygote and homozygous mutant was 28.13% > 32.81 %, 39.06% in COPD group and 32.14 %, 39.39% ^ 28.57% in control group.4 > The frequency of polymorphic genotypes of mEH exon4 showed no difference between the COPD group and the control group:mEH exon4 homozygous wild-type^ heterozygote and homozygous mutant was 84.38 %> 12.5%> 3.12% in COPD group and 76.79%^ 16.06%^ 6.25% in control group^ HO-1 STR polymorphism and cigarette smoking played a positive interactive role in the development of COPD. 6^ TNF- a -308 SNP polymorphism and cigarette smoking played an positive interactive role in the development of COPDo 7^ HO-1 STR polymorphism and TNF- a -308 SNP Polymorphism have no interaction in COPD.Conclusion: 1 n Genetic polymorphism in HO-1 promoter is the risk factor of COPD and there is a positive interaction between HO-1 STR polymorphism and smoking..2> TNF-a-308 SNP polymorphism is associated with development of COPD in Han nationality of China which has a positive interaction with smoking.3-x HO-1 STR polymorphism and TNF- a -308 SNP polymorphism have no interaction inC0PD.4 n Genetic polymorphism in mEH exon 3(Tyrll3His) and exon 4 (Hisl39Arg)is not associated with development of COPD in Han nationality of China.