The role of WWOX polymorphisms on COPD susceptibility and pulmonary function traits in Chinese: a case-control study and family-based analysis.
The role of WWOX polymorphisms on COPD susceptibility and pulmonary function traits in Chinese: a case-control study and family-based analysis.
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WWOX 多态性对中国人 COPD 易感性和肺功能特征的作用：病例对照研究和基于家系的分析。
DOI：
10.1038/srep21716
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发表时间：
2016-02-23
影响因子：
4.6
通讯作者：
Lu J
中科院分区：
文献类型：
--
作者：
Xie C;Chen X;Qiu F;Zhang L;Wu D;Chen J;Yang L;Lu J
含WW结构域氧化还原酶（WWOX）基因中的单核苷酸多态性（SNP）最近被确定为肺功能的数量性状位点，因此很可能是慢性阻塞性肺疾病（COPD）的易感生物标志物。然而，WWOX基因的SNP与COPD发病风险之间的关联仍不明确。在此，我们通过开展一项包含1511例COPD患者和1677名对照的双中心病例对照研究，以及一项涵盖95个核心家系的家系分析，对WWOX基因的5个SNP（即rs10220974 C>T、rs3764340 C>G、rs12918952 G>A、rs383362 G>T、rs12828 G>A）与COPD发病风险之间的关联，以及这些位点在COPD家系中的遗传倾向进行了检验。我们发现，SNP rs383362 G>T与COPD发病风险增加显著相关，且呈T等位基因数量依赖性（优势比[OR]=1.30，95%置信区间[CI]=1.11 - 1.52）。与G等位基因相比，T等位基因更容易过度传递给患病子女和同胞（Z = 2.900，P = 0.004）。此外，与rs383362 GG携带者相比，rs383362 T携带者的一秒用力呼气容积/用力肺活量（FEV1/FVC）、FEV1/预测FEV1以及年FEV1也显著降低。对于其他SNP，未观察到与COPD及肺功能的显著关联。综上所述，我们的数据表明，WWOX基因的SNP rs383362 G>T在COPD遗传中发挥作用。
Single nucleotide polymorphisms (SNPs) in the WW domain containing oxidoreductase (WWOX) gene were recently identified to be quantitative trait loci for lung function and thus likely to be susceptible biomarkers for COPD. However, the associations between WWOX SNPs and COPD risk are still unclear. Here, by conducting a two-center case-control study including 1511 COPD cases and 1677 controls and a family-based analysis comprising 95 nuclear pedigrees, we tested the associations between five SNPs that are rs10220974C >T, rs3764340C >G, rs12918952G >A, rs383362G >T, rs12828G >A of WWOX and COPD risk as well as the hereditary inclination of these loci among COPD families. We found that the SNP rs383362G >T was significantly associated with an increased risk of COPD in a T allele-number dependent-manner (OR = 1.30, 95%CI = 1.11 - 1.52). The T allele was more prone to over transmit to sick children and sibs than the G allele (Z = 2.900, P = 0.004). Moreover, the forced expiratory volume in one second/forced vital capacity (FEV1/FVC), FEV1/predicted-FEV1 and annual FEV1 also significantly decreased in the rs383362T carriers compared to the rs383362GG carriers. For other SNPs, no significant association was observed for COPD and pulmonary function. Taken together, our data demonstrated that the SNP rs383362G >T of WWOX plays a role in COPD inheritance.