ADAM33基因单核苷酸多态性及单体型与慢性阻塞性肺疾病的关联性研究

Association between single nucleotide polymorphisms and haplotypes in ADAM33 gene and chronic obstructive pulmonary disease

目的探讨中国华北地区汉族人群ADAM33基因S1、S2位点单核苷酸多态性及单体型与慢性阻塞性肺疾病（COPD）及肺功能的关联性。方法应用DNA直接测序的方法，对90例COPD患者和90名健康对照者的ADAM33基因S1、S2位点基因型进行检测；应用SHEsis在线软件构建单体型并进行单体型关联分析。结果①病例组和对照组中S1位点基因型及等位基咽频率分布比较差异无统计学意义（P〉0．05），S2位点基因型及等位基因频率分布比较差异有统计学意义（P〈0．05）。②Logistic回归分析表明：ADAM33基因S1位点不同基因型COPD发生的相对危险度比较差异无统计学意义（P〉0．05）；S2位点不同基因型COPD发生的相对危险度比较，差异有统计学意义（P〈0．05），其中G／G＋C／G基因型的OR值为2．364（95％CI1．251～4．466）。③COPD病例组S2位点基因型与肺功能相关临床指标的关系显示：3种基因型FEV。％预计值比较差异无统计学意义而FEV1／FVC比较差异有统计学意义，其中G／G基因型与C／C、C／G基因型相比FEV1／FVC下降更明显。④SHEsis在线软件对S1、S2位点进行单体型分析结果显示，单体型CG在COPD组和对照组中比较差异有统计学意义（P〈0．05）。结论在中国华北地区汉族人群中，ADAM33基因与COPD的易感性有关，但与疾病的严重程度无关。

Objective To investigate whether polymorphisms and haplotypes of S1,S2 locus alleles in ADAM33 gene has any bearing on chronic obstructive pulmonary disease （COPD） and lung function in Han population of northern China. Methods The genotypes of S1,S2 locus alleles in 90 COPD patients and 90 healthy controls were tested with PCR-direct sequeneing analysis. Haplotypes and their frequencies were established and analyzed by SHEsis online software. Results @There was no significant difference between the COPD group and the control group in the frequencies of S1 locus genotypes and alleles （ P 〈0.05）. There was a significant difference between the COPD group and the control group in the frequencies of S2 locus genotypes and alleles （ P 〈0.05）. Q Logistic regression analysis showed： there was not statistically significant difference in the relative risk of COPD in S1 locus genotype （ P 〈0.05）. There was a statistically significant difference in the relative risk of COPD in S2 locus genotype （ P 〈0.05 ）, and the odds ratio （ OR ） of G/G＋C/G genotype was 2. 364 （95% CI 1. 251-4. 466）. @In COPD group, the relationship between ADAM33 gene S2 locus genotype and clinical parameters of lung function display：the difference of FEV： in genotypes was no statistically significant,but the difference of FEV1/FVC in genotypes was statistically significant, and G,/G genotype with FEV~/FVC decline was more significantly than C/C, C/G genotype. @SHEsis online software analysis for S1, S2 loci 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 polymorphism in ADAM33 gene have association with the susceptibility to COPD, and have no association with the severity of COPD.