Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Respir Res. 2010 May 20;11(1):60. doi: 10.1186/1465-9921-11-60.
Multidrug resistance-associated protein-1 (MRP1) protects against oxidative stress and toxic compounds generated by cigarette smoking, which is the main risk factor for chronic obstructive pulmonary disease (COPD). We have previously shown that single nucleotide polymorphisms (SNPs) in MRP1 significantly associate with level of FEV1 in two independent population based cohorts. The aim of our study was to assess the associations of MRP1 SNPs with FEV1 level, MRP1 protein levels and inflammatory markers in bronchial biopsies and sputum of COPD patients.
Five SNPs (rs212093, rs4148382, rs504348, rs4781699, rs35621) in MRP1 were genotyped in 110 COPD patients. The effects of MRP1 SNPs were analyzed using linear regression models.
One SNP, rs212093 was significantly associated with a higher FEV1 level and less airway wall inflammation. Another SNP, rs4148382 was significantly associated with a lower FEV1 level, higher number of inflammatory cells in induced sputum and with a higher MRP1 protein level in bronchial biopsies.
This is the first study linking MRP1 SNPs with lung function and inflammatory markers in COPD patients, suggesting a role of MRP1 SNPs in the severity of COPD in addition to their association with MRP1 protein level in bronchial biopsies.
多药耐药相关蛋白 1（MRP1）可保护机体免受由吸烟产生的氧化应激和有毒化合物的影响，而吸烟是慢性阻塞性肺疾病（COPD）的主要危险因素。我们之前的研究表明，MRP1 中的单核苷酸多态性（SNPs）与两个独立的基于人群的队列中的 FEV1 水平显著相关。本研究旨在评估 MRP1 SNPs 与 COPD 患者支气管活检和痰中 FEV1 水平、MRP1 蛋白水平和炎症标志物的相关性。
对 110 例 COPD 患者中的 5 个 MRP1 SNPs（rs212093、rs4148382、rs504348、rs4781699、rs35621）进行基因分型。使用线性回归模型分析 MRP1 SNPs 的影响。
一个 SNP（rs212093）与更高的 FEV1 水平和更少的气道壁炎症相关。另一个 SNP（rs4148382）与较低的 FEV1 水平、诱导痰中更多的炎症细胞以及支气管活检中更高的 MRP1 蛋白水平相关。
这是首个将 MRP1 SNPs 与 COPD 患者的肺功能和炎症标志物联系起来的研究，表明 MRP1 SNPs 除了与支气管活检中的 MRP1 蛋白水平相关外，还可能与 COPD 的严重程度有关。
