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. 2010Mar 1;181(5):486-93.
doi：10.1164/rccm.200909-1364oc。 Epub 2009 Dec 10.

The 15q24/25 susceptibility variant for lung cancer and chronic obstructive pulmonary disease is associated with emphysema

Diether Lambrechts1, 伊恩·布斯施特（Ian Buysschaert）, Pieter Zanen, Johan Coolen, Natacha Lays, 哈利·库彭斯, 哈利J M Groen, Walter Dewever, Rob J van Klaveren, Johny Verschakelen, Cisca Wijmenga, Dirkje S Postma, Marc Decramer, Wim Janssens
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The 15q24/25 susceptibility variant for lung cancer and chronic obstructive pulmonary disease is associated with emphysema

Diether Lambrechtset al. Am J呼吸危机护理医学. .

抽象的

Rationale:全基因组关联研究已经确定了15q24/25染色体的烟碱乙酰胆碱受体（NACHR）中的遗传变异，是尼古丁依赖性，肺癌和慢性阻塞性肺疾病（COPD）的风险。然而，通过肺活量测定法评估支气管阻塞，通常用于诊断COPD，但无法检测到肺气肿。

目标：To determine the association of the 15q24/25 locus with emphysema.

方法：The rs1051730 variant on 15q24/25 was genotyped in two independent white cohorts of 661 and 456 heavy smokers. Participants underwent pulmonary function tests and computed tomography (CT) of the chest, and took questionnaires assessing smoking behavior and health status.

Measurements and main results:RS1051730 A-Allele与FEV（1）的减少相关，并增加了支气管阻塞的易感性，其比值比（OR）为1.33（95％置信区间[CI] = 1.11-1.61; P = 0.0026）。在这两项研究中，观察到了RS1051730 A-Allele与肺扩散能力（DL（CO））与单位肺泡体积（KCO）的扩散能力之间的相关性。一致地，RS1051730 A-Allele赋予了CT评估的肺气肿风险增加（P = 0.0097和P = 0.019），合并为1.39（CI = 1.15-1.68; P = 0.00051）。基于CT上量化的密度的视觉肺气肿评分和分数在A-Allele载体中更为明显，表明RS1051730与肺气肿的严重程度相关。

Conclusions:The 15q24/25 locus in nAChR is associated with the presence and severity of emphysema. This association was independent of pack-years smoking, suggesting that nAChR is causally involved in alveolar destruction as a potentially shared pathogenic mechanism in lung cancer and COPD.

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