Susceptibility genes for rapid decline of lung function in the Lung Health Study
Susceptibility genes for rapid decline of lung function in the Lung Health Study
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DOI：
10.1164/ajrccm.163.2.2006158
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发表时间：
2001-02-01
影响因子：
24.7
通讯作者：
Paré, PD
中科院分区：
文献类型：
--
作者：
Sandford, AJ;Chagani, T;Paré, PD
导致慢性阻塞性肺疾病（COPD）遗传易感性的基因在很大程度上仍然未知。我们假设吸烟者肺功能下降的速率差异很大，这将是检测导致COPD严重程度的基因的一个可靠表型。在NHLBI肺健康研究中，我们从随访5年的吸烟者中选择了283名快速下降者（Δ FEV 1 = -154 +/- 3 ml/yr）和308名非下降者（Δ FEV 1 = + 15 +/- 2 ml/yr）。FEV 1的快速下降与α（1）-抗胰蛋白酶基因的MZ基因型相关（比值比[OR] = 2.8，p = 0.03）。COPD家族史与MZ的组合的这种关联更强（OR = 9.7，p = 0.03）。这些数据表明，MZ基因型导致肺功能下降的速度增加，并与其他家族因素相互作用。微粒体环氧化物水解酶（mEH）基因的单倍型频率在快速下降者和非下降者之间存在显著差异（p = 0.03）。CORD家族史与His（113）/His（139）mEH单倍型纯合性的组合也与肺功能快速下降相关（OR = 4.9，p = 0.04）。α（1）-抗胰蛋白酶S和3'多态性、维生素D结合蛋白亚型和肿瘤坏死因子（TNF-α G-308 A和TNF-β A252 G）多态性与肺功能下降率无关。
The genes that contribute to the genetic susceptibility to chronic obstructive pulmonary disease (COPD) remain largely unknown. We hypothesized that widely divergent rates of decline in lung function in smokers would be a robust phenotype for detection of genes that contribute to COPD severity. We selected 283 rapid decliners (Delta FEV1 = -154 +/- 3 ml/yr) and 308 nondecliners (Delta FEV1 = + 15 +/- 2 ml/yr) from among smokers followed for 5 yr in the NHLBI Lung Health Study. Rapid decline of FEV1 was associated with the MZ genotype of the alpha (1)-antitrypsin gene (odds ratio [OR] = 2.8, p = 0.03). This association was stronger for a combination of a family history of COPD with MZ (OR = 9.7, p = 0.03). These data suggest that the MZ genotype results in an increased rate of decline in lung function and interacts with other familial factors. Haplotype frequencies of the microsomal epoxide hydrolase (mEH) gene were significantly different between rapid decliners and nondecliners (p = 0.03). A combination of a family history of CORD with homozygosity for the His(113)/His(139)mEH haplotype was also associated with rapid decline of lung function (OR = 4.9, p = 0.04). The alpha (1)-antitrypsin S and 3' polymorphisms, vitamin D-binding protein isoforms, and tumor necrosis factor (TNF-alpha G-308A and TNF-beta A252G) polymorphisms were not associated with rate of decline of lung function.