Department of Internal Medicine and Environmental Health Center, Kangwon National University, Chuncheon, Korea.
Department of Pharmacology, Tissue Injury Defense Research Center, College of Medicine, Ewha Womans University, Seoul, Korea.
J Korean Med Sci. 2018 Feb 12;33(7):e56. doi: 10.3346/jkms.2018.33.e56.
Chronic obstructive pulmonary disease (COPD) is a debilitating lung disease. To date, a large number of clinical studies have been conducted to investigate the association between genetic variations and COPD. However, little is known regarding the genetic susceptibility of Koreans to this disease. MER receptor tyrosine kinase (MERTK) plays important roles in the inhibition of inflammation and in the clearance of apoptotic cells. Here, we investigated the association between genetic variations in MERTK and the development of COPD in Koreans.
We conducted genetic analysis of MERTK using genomic DNA samples from 87 patients with COPD and 88 healthy controls and compared the frequency of each variation or haplotype between the patient and control groups. Subsequently, the effect of each variation was evaluated using in vitro assays.
Ten variations were identified in this study, four of them for the first time. In addition, we found that the frequency of each variation or haplotype was comparable between the patient and control groups. However, we observed that the frequency for the wild-type haplotype was higher in the control group, compared to that in the group of patients with COPD, in the subgroup analysis of current smokers, although the difference was not statistically significant (P = 0.080). In in vitro assays, we observed that none of the variations affected the activity of the promoter or the expression of MERTK.
Our findings indicate that the susceptibility to COPD is not related to the genetic variations or haplotypes of MERTK in Koreans.
慢性阻塞性肺疾病（COPD）是一种使人虚弱的肺部疾病。迄今为止，已经进行了大量的临床研究来探讨遗传变异与 COPD 之间的关系。然而，对于韩国人患这种疾病的遗传易感性知之甚少。MERT 受体酪氨酸激酶（MERTK）在抑制炎症和清除凋亡细胞方面发挥着重要作用。在这里，我们研究了 MERTK 基因变异与韩国人 COPD 发病之间的关系。
我们使用来自 87 名 COPD 患者和 88 名健康对照者的基因组 DNA 样本对 MERTK 进行了基因分析，并比较了患者组和对照组中每个变异或单倍型的频率。随后，使用体外试验评估了每个变异的作用。
在这项研究中发现了 10 个变异，其中 4 个是首次发现。此外，我们发现每个变异或单倍型的频率在患者组和对照组之间无差异。然而，我们观察到，在亚组分析中，与 COPD 患者组相比，在当前吸烟者中，对照组的野生型单倍型频率更高，尽管差异无统计学意义（P=0.080）。在体外试验中，我们观察到没有一个变异影响启动子的活性或 MERTK 的表达。
我们的研究结果表明，韩国人 COPD 的易感性与 MERTK 的遗传变异或单倍型无关。
