Four SNPs in the CHRNA3/5 alpha-neuronal nicotinic acetylcholine receptor subunit locus are associated with COPD risk based on meta-analyses.
Four SNPs in the CHRNA3/5 alpha-neuronal nicotinic acetylcholine receptor subunit locus are associated with COPD risk based on meta-analyses.
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DOI：
10.1371/journal.pone.0102324
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Ma H
中科院分区：
文献类型：
--
作者：
Cui K;Ge X;Ma H
在一项基于挪威人群的研究中，α-神经元烟碱乙酰胆碱受体亚单位（CHRNA 3/5）的几个单核苷酸多态性（SNP）被确定与慢性阻塞性肺疾病（COPD）相关。然而，随后的研究结果一直存在争议，特别是在招募亚洲人的研究中。在本研究中，我们进行了全面的检索和荟萃分析，以确定CHRNA 3/5基因座中COPD的易感性SNP。进行了全面的文献检索，以查找已报告CHRNA 3/5位点的SNP与COPD风险之间相关性的研究。以主要等位基因或基因型作为参照组，计算每个SNP的合并优势比（OR）和95%置信区间（CI）。除了发表偏倚外，还评估了个体研究对汇总指标的影响。本分析共纳入了12篇文章和14项合格研究。评估CHRNA 3/5基因座中的4个SNP与COPD之间的关联，包括rs 1051730、rs 8034191、rs6495309和rs 16969968。在等位基因（rs 1051730：OR = 1.14，95%CI = 1.10-1.18; rs 8034191：OR = 1.29，95%CI = 1.18-1.41; rs6495309：OR = 1.26，95%CI = 1.09-1.45; rs 16969968：OR = 1.27，95%CI = 1.17-1.39）和基因型模型下，确定了4个SNP与COPD之间的显著关联。 针对rs 1051730进行的亚组分析显示，该SNP与非亚洲人的COPD风险之间存在显着相关性（OR = 1.14，95%CI = 1.10-1.18），但与亚洲人的COPD风险无关（OR = 1.23，95%CI = 0.91-1.67）。 在调整多个变量（包括年龄和吸烟状况）后，rs 1051730和rs6495309也与COPD显著相关。我们的研究结果表明，CHRNA 3/5位点的4个SNP与COPD风险相关。Rs 1051730与非亚洲人的COPD特别相关，但其在亚洲人中的作用仍需验证。需要进行额外的研究来评估rs6495309对COPD的影响。尽管rs 1051730和rs6495309被证明是COPD的独立风险因素，但应进行验证研究。
Several single nucleotide polymorphisms (SNPs) in an α-neuronal nicotinic acetylcholine receptor subunit (CHRNA3/5) were identified to be associated with chronic obstructive pulmonary disease (COPD) in a study based on a Norwegian population. However, results from subsequent studies have been controversial, particularly in studies recruiting Asians. In the present study, we conducted a comprehensive search and meta-analyses to identify susceptibility SNPs for COPD in the CHRNA3/5 locus. A comprehensive literature search was conducted to find studies that have reported an association between SNPs in the CHRNA3/5 locus and COPD risk. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) for each SNP were calculated with the major allele or genotype as the reference group. The influence of individual studies on pooled measures was assessed, in addition to publication bias. A total of 12 articles with 14 eligible studies were included in this analysis. Association between 4 SNPs in the CHRNA3/5 locus and COPD was evaluated and included rs1051730, rs8034191, rs6495309, and rs16969968. Significant associations between the 4 SNPs and COPD were identified under allele (rs1051730: OR = 1.14, 95%CI = 1.10–1.18; rs8034191: OR = 1.29, 95%CI = 1.18–1.41; rs6495309: OR = 1.26, 95%CI = 1.09–1.45; rs16969968: OR = 1.27, 95%CI = 1.17–1.39) and genotype models. Subgroup analysis conducted for rs1051730 showed a significant association between this SNP and COPD risk in non-Asians (OR = 1.14, 95%CI = 1.10–1.18), but not Asians (OR = 1.23, 95%CI = 0.91–1.67). Rs1051730 and rs6495309 were also significantly associated with COPD after adjusting for multiple variables, including age and smoking status. Our results indicate that 4 SNPs in the CHRNA3/5 locus are associated with COPD risk. Rs1051730 was particularly associated with COPD in non-Asians, but its role in Asians still needs to be verified. Additional studies will be necessary to assess the effect of rs6495309 on COPD. Although rs1051730 and rs6495309 were shown to be independent risk factors for COPD, validation studies should be performed.
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