Hersh Craig P, DeMeo Dawn L, Silverman Edwin K
Channing Laboratory, Center for Genomic Medicine, and Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Proc Am Thorac Soc. 2008 May 1;5(4):486-93. doi: 10.1513/pats.200706-078ET.
Although a hereditary contribution to emphysema has been long suspected, severe alpha1-antitrypsin deficiency remains the only conclusively proven genetic risk factor for chronic obstructive pulmonary disease (COPD). Recently, genome-wide linkage analysis has led to the identification of two promising candidate genes for COPD: TGFB1 and SERPINE2. Like multiple other COPD candidate gene associations, even these positionally identified genes have not been universally replicated across all studies. Differences in phenotype definition may contribute to nonreplication in genetic studies of heterogeneous disorders such as COPD. The use of precisely measured phenotypes, including emphysema quantification on high-resolution chest computed tomography scans, has aided in the discovery of additional genes for clinically relevant COPD-related traits. The use of computed tomography scans to assess emphysema and airway disease as well as newer genetic technologies, including gene expression microarrays and genome-wide association studies, has great potential to detect novel genes affecting COPD susceptibility, severity, and response to treatment.
尽管长期以来一直怀疑肺气肿存在遗传因素，但严重的α1抗胰蛋白酶缺乏症仍然是慢性阻塞性肺疾病（COPD）唯一经确凿证实的遗传风险因素。最近，全基因组连锁分析已导致鉴定出两个有前景的COPD候选基因：TGFB1和SERPINE2。与许多其他COPD候选基因关联一样，即使是这些通过定位鉴定的基因也并非在所有研究中都能得到普遍验证。表型定义的差异可能导致在COPD等异质性疾病的遗传研究中无法重复验证。使用精确测量的表型，包括在高分辨率胸部计算机断层扫描上对肺气肿进行量化，有助于发现与临床相关的COPD相关性状的其他基因。使用计算机断层扫描来评估肺气肿和气道疾病以及更新的遗传技术，包括基因表达微阵列和全基因组关联研究，在检测影响COPD易感性、严重程度和治疗反应的新基因方面具有巨大潜力。
