Association Between Single Nucleotide Polymorphisms And Haplotypes In ADAM33Gene And Chronic Obstructive Pulmonary Disease

[Objective]To investigate whether polymorphisms and haplotypes in ADAM33gene are associated with chronic obstructive pulmonary disease (COPD) and lung function in Han population of northern China. And to identify if ADAM33gene is the susceptibility gene of COPD and provide the new theoretical basis for describing the pathogenesis of COPD.[Methods]1. According to the COPD diagnosis and treatment guidelines (revised edition in2007) formulated by the respiratory disease branch of Chinese Medical Association branch, we selected90COPD patients diagnosed in Taiyuan City Hospital Department of respiratory branch as the case group and90healthy individuals in the same period as the control group. All subjects were Han population of northern China and were through detailed medical history inquiry, physical examination, pulmonary function tests and chest radiography examination excluded from the respiratory diseases, such as bronchial asthma, bronchiectasis, pulmonary tuberculosis, pulmonary interstitial fibrosis, diffuse panbronchiolitis, bronchial lung cancer.2.We collected venous blood2ml from all subjects and then extracted DNA. ADAM33gene fragments containing S1、S2locus alleles were amplified by PCR. And Using PCR-direct sequeneing analysis tested the genotypes of the fragments and then calculated the genotype frequency and allele frequencies. Haplotypes and their frequencies were established and analyzed by SHEsis online software.[Results](1) there was no significant difference between the COPD group and the control group in the frequencies of S1locus genotypes and alleles (P>0.05); there was a significant difference between the COPD group and the control group in the frequencies of S2locus genotypes and alleles (P<0.05). (2) Logistic regression analysis showed:there was not statistically significant difference in the relative risk of COPD in S1locus genotype(P>0.05); there was a statistically significant difference in the relative risk of COPD in S2locus genotype(P <0.05), and the odds ratio(OR)of G/G+C/G genotype was2.364(95%CI1.251～4.466).(3) In COPD group, the relationship between ADAM33gene S2locus genotype and clinical parameters of lung function display:the difference of FEV1%in genotypes was no statistically significant,but the difference of FEV1/FVC in genotypes was statistically significant,and G/G genotype with FEV1/FVC decline was more significantly than C/C、C/G genotype.(4) SHEsis online software analysis for S1、S2loci haplotype showed that haplotype C/G in COPD and control groups was statistically significant difference(P <0.05).[Conclusions]In Han population of northern China, the polymorphisms and haplotypes in ADAM33gene have association with the susceptibility to COPD, and have no association with the severity of COPD.