Alpha-1 Antitrypsin MZ Heterozygosity Is an Endotype of Chronic Obstructive Pulmonary Disease
Alpha-1 Antitrypsin MZ Heterozygosity Is an Endotype of Chronic Obstructive Pulmonary Disease
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DOI：
10.1164/rccm.202106-1404oc
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发表时间：
2022-02-01
影响因子：
24.7
通讯作者：
Hersh, Craig P.
中科院分区：
文献类型：
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作者：
Ghosh, Auyon J.;Hobbs, Brian D.;Hersh, Craig P.
理论基础：多项研究表明，AAT(α-1抗胰蛋白酶)Z等位基因杂合子携带者患慢性阻塞性肺疾病(COPD)的风险增加。目的：探讨MZ COPD患者与MM COPD患者是否有不同的临床特征。方法：采用全基因组测序方法，对3个独立研究中的MZ COPD患者和MM COPD患者进行SERPINA 1基因分型。在每项研究中，我们比较了患有COPD的MM受试者和患有COPD的MZ受试者的结果，并将结果合并到荟萃分析中。我们进行了纵向和生存分析，以比较MM和MZ受试者随时间推移患有COPD的结果。测量和主要结果：我们在三项研究中包括290名患有COPD的MZ受试者和6184名患有COPD的MM受试者。与MM患者相比，MZ患者的FEV1预测百分比较低，而胸部CT扫描显示肺气肿的数量较多。在Meta分析中，FEV1降低3.9%(95%可信区间[CI]，-6.55%至-1.26%)和肺气肿(肺衰减面积百分比
Rationale: Multiple studies have demonstrated an increased risk of chronic obstructive pulmonary disease (COPD) in heterozygous carriers of the AAT (alpha-1 antitrypsin) Z allele. However, it is not known if MZ subjects with COPD are phenotypically different from noncarriers (MM genotype) with COPD.Objectives: To assess if MZ subjects with COPD have different clinical features compared with MM subjects with COPD.Methods: Genotypes of SERPINA 1 were ascertained by using whole-genome sequencing data in three independent studies. We compared outcomes between MM subjects with COPD and MZ subjects with COPD in each study and combined the results in a meta-analysis. We performed longitudinal and survival analyses to compare outcomes in MM and MZ subjects with COPD over time.Measurements and Main Results: We included 290 MZ subjects with COPD and 6,184 MM subjects with COPD across the three studies. MZ subjects had a lower FEV1 % predicted and greater quantitative emphysema on chest computed tomography scans compared with MM subjects. In a meta-analysis, the FEV1 was 3.9% lower (95% confidence interval [CI], -6.55% to -1.26%) and emphysema (the percentage of lung attenuation areas