Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan.
Department of Premier Preventive Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan.
Lung. 2019 Oct;197(5):559-564. doi: 10.1007/s00408-019-00251-2. Epub 2019 Jul 11.
Several studies have reported that single nucleotide polymorphisms (SNPs) in the gene encoding NF-E2-related factor 2 (Nrf2) contribute to airflow limitations in smokers without COPD. Although small airway lesions and emphysema contribute cooperatively to airflow limitation, the relationship between Nrf2 SNPs and the development of emphysema in smokers without COPD is not well understood.
Healthy subjects who underwent an annual health checkup with computed tomography (CT) of the chest at Osaka City University Hospital were prospectively recruited. The percentage of low-attenuation area (%LAA) on chest CT was quantified, and correlations between %LAA, Nrf2 SNP [rs6726395 (G/A)] genotypes, and clinical characteristics were examined.
A total of 245 subjects without COPD [non-/light-smoker: 153 (62.4%) and smoker: 92 (37.6%)] were enrolled. The %LAA in the upper lung field was higher than that in the lower lung field (p < 0.001). The %LAA in smokers was significantly higher than that in non-/light-smokers (p = 0.021). The %LAA showed significant but weak correlation with age in all subjects (r = 0.141, p = 0.028). Divided by genotype, the %LAA of the upper lung field was significantly correlated with age in smokers with genotype GG (wild type) (r = 0.333, p = 0.022), but was not significantly correlated with age in smokers with genotype AG/AA. These correlations were not observed in non-/light smokers.
A polymorphism rs6726395 in Nrf2 can contribute to the development of emphysema-associated aging in smokers. The Nrf2 SNP may be a predictive factor for smoking-induced emphysema, and genotyping of Nrf2 SNP may serve as biomarker for emphysema prevention.
几项研究报告称，编码核因子红细胞 2 相关因子 2（Nrf2）的单核苷酸多态性（SNP）导致非 COPD 吸烟者的气流受限。虽然小气道病变和肺气肿协同导致气流受限，但 Nrf2 SNP 与非 COPD 吸烟者肺气肿的发展之间的关系尚不清楚。
前瞻性招募在大阪城市大学医院接受年度健康检查并进行胸部计算机断层扫描（CT）的健康受试者。定量胸部 CT 上的低衰减区（%LAA）百分比，并检查%LAA、Nrf2 SNP[rs6726395（G/A）]基因型与临床特征之间的相关性。
共纳入 245 名无 COPD 的受试者[非吸烟者/轻度吸烟者：153（62.4%）和吸烟者：92（37.6%）]。上肺野的%LAA 高于下肺野（p<0.001）。吸烟者的%LAA 明显高于非吸烟者/轻度吸烟者（p=0.021）。在所有受试者中，%LAA 与年龄呈显著但弱相关（r=0.141，p=0.028）。按基因型分组，上肺野的%LAA 与基因型 GG（野生型）的吸烟者的年龄呈显著相关（r=0.333，p=0.022），但与基因型 AG/AA 的吸烟者的年龄无显著相关性。这些相关性在非吸烟者/轻度吸烟者中没有观察到。
Nrf2 中的一个 SNP rs6726395 可能导致吸烟者肺气肿相关的衰老。Nrf2 SNP 可能是吸烟引起的肺气肿的预测因子，Nrf2 SNP 的基因分型可能作为肺气肿预防的生物标志物。
