The Associated Study Between Genetic Polymorphism Of TNF-α,IL-6 And Chronic Obstructive Pulmonary Disease

The pathogenesis of chronic obstructive pulmonary disease (COPD) involve genetically factors and environmental factors. Tumor necrosis factor-α(TNF-α) and Interleukin-6(IL-6) are considered to play a role in the pathogenesis of COPD. So we detected the relations on individual susceptibility between the polymorphisms in gene of TNF-αpromoter region at+489,IL-6 promoter region at-572 and COPD by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism(PCR-RFLP).Materials and Methods:The research design was a case-control study.After collecting the peripheral blood of 60 COPD patients and 62 controls in Han nationally of Fenyang region, Shanxi province,we extracted their genomic DNA.The polymorphisms in gene of TNF-αpromoter region at+489 and IL-6 promoter region at-572 in the patents and controls were performed by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP).We detected the genotype by agarose gel electrophoresis and analyzed their genotype frequencies and allele frequencies.The data was analyzed by sofeware of spss16.0, the data of age and pulmonary function were analyzed by two independent t-test, the date of gender, constitution ratio of smoking history and smoking index,frequencies of genetype and allele were analyzed by Chi-square test or Fisher exact probability test, odds ratio (OR) and 95% confidence interval (95%CI) were calculated the potential risk for developing COPD,the interaction between risk factors and COPD was analyzed by additive model,which were smoking and genetic polymorphisms.Results:1.The gender distribution and mean age did not show significant differences,but both FEV1% and FEV1/FVC showed significant differences between patients and controls.2.The constitution ratio of smoking history and smoking index showed significant differences between patients and controls,and compared with non-smokers,smokers increased gradually the risk for developing COPD with the smoking index increasing.3.The amplification of TNF-α+489 was 551bp and there were three genotypes after cutting by incision enzyme,on the electropherogram G/G genotype was three bright bars(111bp,159bp,281bp), G/Agenotype was four bright bars(111bp,159bp,281bp,392bp),and A/A genotype was two bright bars(159bp,392bp). The amplification of IL-6-572 was 163bp and there were three genotypes after cutting by incision enzyme,on the electropherogram C/C genotype was one bright bar(163bp), C/Ggenotype was three bright bars(163bp,101bp,62bp),and G/G genotype was two bright bars(101bp,62bp).4.The genotype frequencies of TNF-α+489 and IL-6-572 were all in Hardy-Weinberg equilibrium,so two groups were representative.5. There was no significant differences in the genotype frequencies of TNF-α+489 between patients and controls,but the frequencies of G/G genotype and non-G/G(GA,A/A) genotype had significant differences between two groups,and the frequencies of allele G and A were significantly different between two groups.Subjects with allele A, compared with allele Qhad a higher risk for developing COPD (OR=2.280).There was no significant differences in the genotype and allele frequencies of IL-6-572 between patients and controls,and the frequencies of C/C genotype and non-C/C (C/G,G/G) genotype had no significant differences,too.6.Compared controls with other Chinese people,there was no significant differences in the genotype and allele frequencies of IL-6-572,so was there between controls and Japanese.But compared controls with Caucasian, there was significant differences in the genotype and allele frequencies of IL-6-572,so was there between controls and American.7.There was no significant differences in the allele A frequencies of TNF-α+489 between smokers and non-smokers of COPD.8.There was no significant differences in the genotype and allele frequencies of TNF-α+489 among four groups of COPD,who were divided into four different level according to pulmonary function.9.Compared with G/G genotype without smoking history, smoker with G/A and A/A genotype had a higher risk for developing COPD significantly(OR=6.500,S>1),smoking and TNF-α+489 single nucleotide polymorphism played a positive interactive role in developing COPD.Conclusions:1. TNF-αpromoter region at+489 single nucleotide polymorphism possibly was associated with COPD in Han nationally of Fenyang region, Shanxi province, TNF-α+489A allele could confer a increased risk of developing COPD.2.Smoking and TNF-α+489 single nucleotide polymorphism could play a positive interactive role in developing COPD.3.There was no significant differences in the IL-6-572 frequencies of genotype and allele between different race, Asian could be similar frequency of IL-6-572 genotype and allele,so could European and American.4.IL-6 promoter region at-572 single nucleotide polymorphism possibly was not significantly associated with COPD in Han nationally of Fenyang region, Shanxi province.