Examining genetic susceptibility in acute exacerbations of COPD.
Examining genetic susceptibility in acute exacerbations of COPD.
复制标题
检查 COPD 急性加重的遗传易感性。
DOI：
10.1136/thoraxjnl-2017-211106
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发表时间：
2018
期刊：
影响因子：
10
通讯作者：
Wan,EmilyS
中科院分区：
文献类型：
--
作者：
Wan,EmilyS
急性加重（AE）显著增加了发病率和死亡率，并占慢性阻塞性肺疾病（COPD）相关直接成本的很大比例。1尽管在人群水平上，AE频率通常随着肺量测定气流阻塞的恶化而增加，但个体经历的加重次数存在相当大的差异。流行病学研究支持存在对AE的“内在易感性”，其独立于肺量测定法上1秒用力呼气量（FEV1）的受损程度。2这促进了对可能导致AE敏感性差异的遗传变异的研究。研究COPD中基因序列变异与AE风险之间相关性的研究概述见表1。迄今为止发表的绝大多数研究都使用了“候选基因”方法，即检查了被认为是加重易感性的合理贡献者的基因中的有限数量的变体。不幸的是，从这些调查中获得的知识往往不一致。研究之间的非重复性或相互矛盾的相关性报告很常见，即使在询问相同的变体时也是如此（如肾上腺素受体β 2基因ARDB 2的研究所示）。这可能是由于（至少部分是由于）偶然发现、研究规模小的效力有限以及统计严谨性不足。基因分型、计算能力和统计方法学的最新进展促进了基于“无假设”基因组学的复杂疾病和性状研究的广泛应用，但文献中明显缺乏使用这种方法的COPD AE风险研究。
Acute exacerbations (AE) contribute significantly to morbidity and mortality, and account for a substantial proportion of the direct costs associated with chronic obstructive pulmonary disease (COPD). 1 Although AE frequency generally increases with worsening spirometric airflow obstruction on the population level, considerable variation in the number of exacerbations experienced by individuals exists. Epidemiological studies support the existence of an ‘intrinsic susceptibility’towards AE which is independent of the degree of impairment in forced expiratory volume in 1 s (FEV1) on spirometry. 2 This has fuelled the search for genetic variants which may contribute to differential susceptibility towards AEs. An overview of studies investigating associations between genetic sequence variants and AE risk in COPD is shown in table 1. The vast majority of studies published to date have used the ‘candidate gene’approach, whereby a limited number of variants in genes felt to be plausible contributors to exacerbation susceptibility are examined. Unfortunately, the body of knowledge arising from these investigations is often inconsistent. Non-replication or conflicting reports of association between studies are common, even when identical variants are interrogated (as exemplified by studies on the adrenoreceptor beta 2 gene, ARDB2). This is likely due, at least in part, to chance findings, limited power from small study sizes and inadequate statistical rigour. Recent advances in genotyping, computing power and statistical methodologies have facilitated the widespread application of ‘hypothesis-free’genomics-based studies of complex diseases and traits, yet studies of AE risk in COPD using this approach have been conspicuously absent from the literature.