Hersh Craig P, DeMeo Dawn L, Reilly John J, Silverman Edwin K
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Respir Res. 2007 Aug 8;8(1):59. doi: 10.1186/1465-9921-8-59.
In the National Emphysema Treatment Trial (NETT), marked variability in response to lung volume reduction surgery (LVRS) was observed. We sought to identify genetic differences which may explain some of this variability.
In 203 subjects from the NETT Genetics Ancillary Study, four outcome measures were used to define response to LVRS at six months: modified BODE index, post-bronchodilator FEV1, maximum work achieved on a cardiopulmonary exercise test, and University of California, San Diego shortness of breath questionnaire. Sixty-four single nucleotide polymorphisms (SNPs) were genotyped in five genes previously shown to be associated with chronic obstructive pulmonary disease susceptibility, exercise capacity, or emphysema distribution.
A SNP upstream from glutathione S-transferase pi (GSTP1; p = 0.003) and a coding SNP in microsomal epoxide hydrolase (EPHX1; p = 0.02) were each associated with change in BODE score. These effects appeared to be strongest in patients in the non-upper lobe predominant, low exercise subgroup. A promoter SNP in EPHX1 was associated with change in BODE score (p = 0.008), with the strongest effects in patients with upper lobe predominant emphysema and low exercise capacity. One additional SNP in GSTP1 and three additional SNPs in EPHX1 were associated (p < 0.05) with additional LVRS outcomes. None of these SNP effects were seen in 166 patients randomized to medical therapy.
Genetic variants in GSTP1 and EPHX1, two genes encoding xenobiotic metabolizing enzymes, were predictive of response to LVRS. These polymorphisms may identify patients most likely to benefit from LVRS.
在国家肺气肿治疗试验（NETT）中，观察到肺减容手术（LVRS）的反应存在显著差异。我们试图确定可能解释这种差异的遗传差异。
在NETT遗传学辅助研究的203名受试者中，使用四项结局指标来定义六个月时对LVRS的反应：改良BODE指数、支气管扩张剂后第一秒用力呼气容积（FEV1）、心肺运动试验中的最大运动量以及加利福尼亚大学圣地亚哥分校气短问卷。对先前显示与慢性阻塞性肺疾病易感性、运动能力或肺气肿分布相关的五个基因中的64个单核苷酸多态性（SNP）进行基因分型。
谷胱甘肽S-转移酶pi（GSTP1）上游的一个SNP（p = 0.003）和微粒体环氧化物水解酶（EPHX1）中的一个编码SNP（p = 0.02）均与BODE评分的变化相关。这些效应在非上叶为主、低运动能力亚组的患者中似乎最为明显。EPHX1中的一个启动子SNP与BODE评分的变化相关（p = 0.008），在上叶为主的肺气肿和低运动能力患者中效应最强。GSTP1中的另外一个SNP和EPHX1中的另外三个SNP与其他LVRS结局相关（p < 0.05）。在随机接受药物治疗的166名患者中未观察到这些SNP效应。
编码外源性物质代谢酶的两个基因GSTP1和EPHX1中的遗传变异可预测对LVRS的反应。这些多态性可能识别出最有可能从LVRS中获益的患者。
