背景:氧化应激基因多态性与慢性阻塞性肺疾病(COPD)风险之间的关系已被广泛研究,但结果存在争议。本研究旨在探讨包括谷胱甘肽S-转移酶(GST)在内的氧化应激基因之间的整体关联,环氧化物水解酶外显子(EPHX),超氧化物歧化酶(SOD),过氧化氢酶(CAT),细胞色素P450系统(CYP)和血红素加氧酶(HO-1)多态性与COPD的风险。
方法:我们搜索了PubMed和EMBASE数据库,以确定研究氧化应激基因多态性与COPD风险之间关联的研究。提取相关数据并使用Revman5.4和STATA12软件进行统计分析。显性遗传模型,隐性模型,共同主导模型,杂合子模型,和等位基因模型进行分析。威尼斯标准和出版偏见进行了访问的可信度和可靠性。
结果:总计,包括14,733例患者和50,570例对照的63篇出版物被纳入荟萃分析。和GSTP1,CAT中的7个SNP,CYP,SOD是迄今为止的首次分析。在我们的研究中,EPHXT113CC等位基因,GSTM1为null,GSTT1为null,GSTP1A313GG和C341TT等位基因,CYP1A1MspIC等位基因,SOD3A213GG等位基因和Ho-1中的L型显示COPD风险增加,尤其是亚洲人。CATC262T中的T等位基因和SOD2Val9Ala中的C等位基因与COPD风险降低有关。为了避免高度异质性和发表偏见,根据HWE和种族进行亚组分析.发表偏倚通过Begg的漏斗图和Egger的检验进行评估,未发现隐性模型的发表偏倚。确定了4种变异,具有与COPD风险相关的流行病学证据。
结论:我们的结果证实氧化应激基因多态性与COPD风险相关。这些发现可以提高人类对这种疾病基因分子水平的认识,并能够早期干预和预防COPD。具有大样本量的精心设计的研究对于阐明这些显著变异与COPD易感性的关联至关重要。
BACKGROUND: The association between the oxidative stress gene polymorphism and chronic obstructive pulmonary disease (COPD) risk has been extensively studied but the results have been controversial. This study aimed to investigate the overall association between the oxidative stress gene including glutathione S-transferase (GST), epoxide hydrolase exon (EPHX), superoxide dismutase (SOD), catalase (CAT), cytochrome P450 system (CYP) and heme oxygenase (HO-1) polymorphism and the risk of COPD.
METHODS: We searched the PubMed and EMBASE database to identify studies that investigated the association between the oxidative stress gene polymorphism and risk of COPD. The relevant data were extracted and statistical analyses were performed using the Revman 5.4 and STATA 12 software. Dominant genetic model, recessive model, co-dominant model, heterozygote model, and allele model were analyzed. Venice criteria and publication bias were conducted to access the credibility and reliability.
RESULTS: In total, 63 publications including 14,733 patients and 50,570 controls were included in the meta-analysis.15 genetic variants of 6 genes were analyzed, and 7 SNPs in GSTP1, CAT, CYP, SOD were first analyses until now. In our study, EPHX T113C C allele, GSTM1 null, GSTT1 null, GSTP1 A313G G and C341T T allele, CYP1A1 MspI C allele, SOD3 A213G G allele and L type in Ho-1 showed increased COPD risk, especially in Asians. T allele in CAT C262T and C allele in SOD2 Val 9 Ala were associated with decreased COPD risk. To avoid high heterogeneity and publications bias, subgroups analysis was performed in accord with HWE and ethnicity. Publication bias was assessed by Begg\'s funnel plots and Egger\'s test, and no publication bias were found for recessive models. 4 variants were identified with strong levels of epidemiological evidence of associations with the COPD risk.
CONCLUSIONS: Our results confirm that oxidative stress gene polymorphism was associated with COPD risk. These finding can improve human understanding of this disease gene molecular level and enable early intervention and prevention of COPD. Well-designed studies with large sample sizes are essential to clarify the association of these significant variants with the susceptibility to COPD.