Department of Respiratory, the Second Affiliated Hospital of Harbin Medical University, Harbin 150081, PR China.
BMC Med Genet. 2009 Dec 10;10:132. doi: 10.1186/1471-2350-10-132.
Chronic obstructive pulmonary disease (COPD) is influenced by both environmental and genetic factors. ADAM33 (a disintegrin and metalloproteinase 33) has been one of the most exciting candidate genes for asthma since its first association with the disease in Caucasian populations. Recently, ADAM33 was shown to be associated with excessive decline of lung function and COPD. The aim of this study was to evaluate the potential relationship between polymorphisms of ADAM33 and COPD in a Han population in northeastern China.
A total of 312 COPD patients and a control group of 319 healthy volunteers were recruited for this study. Eight polymorphic loci (V4, T+1, T2, T1, S2, S1, Q-1, and F+1) of ADAM33 were selected for genotyping. Genotypes were determined by using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.
Statistically significant differences in the distributions of the T2G, T1G, S2C, and Q-1G alleles between patients and controls were observed (P < 0.001, odds ratio (OR) = 2.81, 95% confidence interval (CI) = 2.19-3.61; P < 0.001, OR = 2.60, 95% CI = 2.06-3.30; P = 0.03, OR = 1.31, 95% CI = 1.02-1.69; and P < 0.001, OR = 1.93, 95% CI = 1.50-2.50, respectively). Haplotype analysis showed that the frequencies of the CGGGGAGC, CGGGGAGT, CGGGCAGC, and CGGGGGGC haplotypes were significantly higher in the case group than in the control group (P = 0.0002, 0.0001, 0.0005, and 0.0074, respectively). In contrast, the haplotype CGAAGAGC was more common in the control group than in the case group (P < 0.0001).
These preliminary results suggest an association between ADAM33 polymorphisms and COPD in a Chinese Han population.
慢性阻塞性肺疾病（COPD）受环境和遗传因素的影响。自从 ADAM33（解整合素和金属蛋白酶 33）首次与白种人群的哮喘相关联以来，它一直是最令人兴奋的候选基因之一。最近，ADAM33 被证明与肺功能过度下降和 COPD 有关。本研究旨在评估 ADAM33 多态性与中国东北地区汉族人群 COPD 之间的潜在关系。
本研究共纳入 312 例 COPD 患者和 319 例健康对照者。选择 ADAM33 的 8 个多态性位点（V4、T+1、T2、T1、S2、S1、Q-1 和 F+1）进行基因分型。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法确定基因型。
患者组与对照组在 T2G、T1G、S2C 和 Q-1G 等位基因的分布上存在统计学差异（P<0.001，优势比（OR）=2.81，95%置信区间（CI）=2.19-3.61；P<0.001，OR=2.60，95%CI=2.06-3.30；P=0.03，OR=1.31，95%CI=1.02-1.69；P<0.001，OR=1.93，95%CI=1.50-2.50）。单体型分析显示，病例组中 CGGGGAGC、CGGGGAGT、CGGGGCAGC 和 CGGGGGGC 单体型的频率明显高于对照组（P=0.0002、0.0001、0.0005 和 0.0074）。相反，CGAAGAGC 单体型在对照组中的频率高于病例组（P<0.0001）。
这些初步结果提示 ADAM33 多态性与中国汉族人群 COPD 之间存在关联。
