Lakhdar Ramzi, Denden Sabri, Knani Jalel, Leban Nadia, Daimi Houria, Hassine Mohsen, Lefranc Gérard, Chibani Jemni Ben, Khelil Amel Haj
Biochemistry and Molecular Biology Laboratory, Faculty of Pharmacy, Monastir, Tunisia.
Genet Test Mol Biomarkers. 2010 Dec;14(6):857-63. doi: 10.1089/gtmb.2009.0168. Epub 2010 Oct 9.
It is well known that cigarette smoking is the major risk factor for chronic obstructive pulmonary disease (COPD). However, only 10%-20% of chronic heavy cigarette smokers develop symptomatic disease, which suggests the presence of genetic susceptibility. Microsomal epoxide hydrolase (EPHX1) is an enzyme involved in the protective mechanism against oxidative stress. It has been reported that gene polymorphisms of this enzyme may be associated with variations in EPHX1 activity. In this study, we aimed at investigating the relationship between EPHX1 polymorphisms and susceptibility to COPD in the Tunisian population. EPHX1 exon 3 (rs1051740, Tyr113His) and exon 4 (rs2234922, His139Arg) polymorphisms were genotyped by polymerase chain reaction followed by restriction fragment length polymorphism analysis. These techniques were used to examine a total of 416 Tunisian individuals, including 182 blood donors and a group of 234 COPD patients. All subjects were not related. An increased risk for COPD was observed in subjects with EPHX1 His113-His113 genotype (odds ratio = 2.168; confidence interval 1.098-4.283; p = 0.02386). However, multivariate logistic regression analysis showed no significant relationship between the mutant genotype and the disease after adjustment for sex, age, body mass index, smoking status, and pack-year smoking (odds ratio = 1.524; confidence interval, 0.991-6.058; p = 0.06137). Regarding the two subtypes of COPD, our investigations demonstrated that there is no significant correlation between exon 3 polymorphism and the chronic bronchitis subgroup (p = 0.09034). The relation between exon 3 polymorphism and emphysema was significant in the univariate analysis (p = 0.02257), but no association was found after controlling for classic risk factors (p = 0.06273). In conclusion, our results showed that there is a weak relation between 113His genotype and COPD, and no apparent relation between 139Arg and COPD in the studied Tunisian population.
众所周知，吸烟是慢性阻塞性肺疾病（COPD）的主要危险因素。然而，只有10%-20%的慢性重度吸烟者会出现症状性疾病，这表明存在遗传易感性。微粒体环氧化物水解酶（EPHX1）是一种参与抗氧化应激保护机制的酶。据报道，该酶的基因多态性可能与EPHX1活性的变化有关。在本研究中，我们旨在调查突尼斯人群中EPHX1多态性与COPD易感性之间的关系。通过聚合酶链反应随后进行限制性片段长度多态性分析，对EPHX1外显子3（rs1051740，Tyr113His）和外显子4（rs2234922，His139Arg）多态性进行基因分型。这些技术用于检查总共416名突尼斯人，包括182名献血者和一组234名COPD患者。所有受试者均无亲缘关系。EPHX1 His113-His113基因型的受试者患COPD的风险增加（比值比=2.168；置信区间1.098-4.283；p=0.02386）。然而，多因素逻辑回归分析显示，在对性别、年龄、体重指数、吸烟状况和吸烟包年数进行调整后，突变基因型与疾病之间无显著关系（比值比=1.524；置信区间，0.991-6.058；p=0.06137）。关于COPD的两个亚型，我们的研究表明，外显子3多态性与慢性支气管炎亚组之间无显著相关性（p=0.09034）。在单因素分析中，外显子3多态性与肺气肿之间的关系显著（p=0.02257），但在控制经典危险因素后未发现关联（p=0.06273）。总之，我们的结果表明，在研究的突尼斯人群中，113His基因型与COPD之间存在弱关系，而139Arg与COPD之间无明显关系。
