BACKGROUND:Genetic factors are believed to play a role in the individual susceptibility to chronic obstructive pulmonary disease (COPD). A single nucleotide polymorphism (SNP) of tumour necrosis factor-alpha (TNF-alpha) has been reported but inconsistent results may arise from different populations and phenotypes of COPD. There are only a few published studies of interleukin-13 (IL-13) SNPs on COPD. The SNPs of TNF-alpha and IL-13 have not been studied in the Chinese population. This research was conducted to study the frequencies of IL-13 gene promoter 1055 (IL-13-1055) and TNF-alpha gene-308 polymorphisms in the patients with COPD and to investigate the effect of those genetic polymorphisms on COPD in the Chinese population.METHODS:A cohort of COPD patients and age matched controls were recruited from an inpatient hospital service in Beijing. Venous blood was obtained and genomic DNA was extracted from peripheral blood monocytes using standard method. Genomic DNA was used as a template for amplification by polymerase chain reaction (PCR) to determine the polymorphism at -1055 in the IL-13 gene promoter region. PCR restriction fragment length polymorphism (RFLP) was used to determine polymorphisms in the TNF-alpha gene-308 position. The products were investigated by sequence analysis also.RESULTS:One hundred and eleven COPD patients and 97 controls were studied. Seventy-five cases were current smokers in COPD patients and 36 were current smokers in controls. The frequencies of TT genotype in the IL-13 gene promoter region were 11.7% (13/111) in the COPD group and 13.4% (13/97) in the controls (P = 0.713). However, the OR value of TT genotype was significantly increased to 6.4 (95% CI 1.62 - 25.39) in the smokers with COPD. TT genotype was also positively related to family history of COPD, OR = 7.7 (95% CI 1.37 - 43.80). The frequencies of A allele in the TNF-alpha gene were 5.9% in COPD and 3.1% in controls (P = 0.131). The OR value of A allele was 5.0 (95% CI 1.011 to 25.059) in smokers with COPD.CONCLUSIONS:There is no significant difference in the frequencies of the TT genotype of IL-13-1055 or the A allele of the TNF-alpha between Han Chinese patients with COPD versus control. Thus, it does not appear that these SNPs are independent factors in COPD for Han nationality in Beijing. However, these SNPs may increase the risk of COPD among smokers.

OBJECTIVE:To study the frequencies of interleukin-13 (IL-13) gene promoter 1055 (IL-13-1055) polymorphism in patients with chronic obstructive pulmonary disease (COPD) and to investigate the effect of this genetic polymorphism on COPD in Chinese.METHODS:The polymorphism in 111 COPD patients and 97 controls who had non-obstructive pulmonary disease were studied. Genomic DNA was extracted from peripheral blood mononuclear cells by using standard high-concentration salt method. Genomic DNA was used as a template for amplification by polymerase chain reaction (PCR)-amplification of specific allele (PASA) to determine the polymorphism at -1055 in the IL-13 gene promoter region. The production was investigated by sequence analysis. SPSS was used for statistical analysis. chi(2) test was used to examine the genotype in COPD patients and controls. Logistic regression analysis was used to exclude confounding factors and evaluate the effect of smoking or family history on COPD combining with gene polymorphism.RESULTS:The frequency of TT genotype in COPD was 11.7% (13/111), and 13.4% (13/97) in control group, P = 0.713. P value was increased to 0.244 using logistic regression analysis excluded confounding factors, including age, gender, smoking and combined diseases. TT genotype can increase the risk of smoking to COPD, OR = 6.40 (95% CI: 1.62 - 25.39) when the data was stratified by smoking status. TT genotype was positively related with family history of COPD, OR = 7.67 (95% CI: 1.37 - 43.80) using multiple factors regression analysis to clinic phenotype and TT genotype.CONCLUSION:TT genotype of IL-13-1055 is not an independent factor for COPD in Chinese Han people in Beijing, but increases the risk for smokers to develop COPD and the one who has COPD family history as well.

患者,女,69岁,因咳嗽伴胸闷,气促2月余,于2002年10月20日以"肺肿瘤,胸腔积液"收入院.于2002年9月开始,无诱因出现咳嗽、咳白粘痰、胸闷、活动后气促、喜右侧卧位,伴低热37.6℃,无盗汗、胸痛及咯血.曾在当地医院拍胸片考虑"右肺占位,右侧胸腔积液",曾抽出血性胸水,CT示"右肺中、下叶巨大型占位病变,伴出血囊变,考虑肺癌?肉瘤?畸胎瘤恶性变可能."

Objective To compare the frequencies of tumor necrosis factor -α(TNF-α) gene-308 polymorphism in chronic obstructive pulmonary disease (COPD) patients and controls,to analyze the relationship of this polymorphism with COPD in Chinese.Methods 101 COPD patients and 96 controls who have no airway obstruction were included in this study.Genomic DNA was extracted from peripheral blood samples by using standard method.Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used to determine the polymorphism in the tumor necrosis factor-αgene-308 position.TNF-α G allele can be digested into two fragments by NcoⅠ,while the TNF-α A allele can not be digested.Results There were no significant differences in allele and genotype frequencies between COPD and control.However,in smokers the OR of A allele was higher than that of G allele.Conclusion The polymorphism in TNF-α gene-308 position alone is not associated with COPD,but increase the risk to develop COPD in smokers .