State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510120, Guangdong, China.
Mol Genet Genomics. 2018 Jun;293(3):649-655. doi: 10.1007/s00438-017-1408-z. Epub 2017 Dec 28.
The polymorphisms of cytokine genes has been reported to modulate the individual's susceptibility to environmental stimuli in COPD development. C-X-C motif chemokine 10 (CXCL10) mediates recruitment inflammatory cells such as monocytes. Therefore, it may play a key role in COPD. Here, a case-control study was conducted to evaluate the association between CXCL10 tag-SNPs and COPD risk. Four tag-SNPs including rs4256246, rs4508917, rs56061981, and rs56316945 were identified based on the linkage disequilibrium (LD) analysis in 30 healthy controls. The associations between these four tag-SNPs and COPD risk were further evaluated in 480 COPD cases and 488 controls. We found that the "T" allele of rs56061981 was significantly associated with reducing risk of COPD, while "G" allele of rs56316945 was significantly associated with increasing risk of COPD. SNP rs56316945 was significantly associated with increasing risk of COPD under different models except recessive model after adjusting the sex, age, pack year, and biomass. SNP rs56061981 was significantly associated with decreasing COPD risk under different models except recessive model after adjusting the sex, age, pack year, and biomass. Stratified analysis of smoking status and biomass with SNPs supported rs56061981 may interact with biomass and smoking thus modulate COPD susceptibility and rs56216945 was apparently associated with the severity of pulmonary function of COPD patients. This study suggests that rs56061981 and rs56216945 in CXCL10 gene promoter contribute COPD susceptibility.
细胞因子基因的多态性已被报道可调节个体对 COPD 发展中环境刺激的易感性。C-X-C 基序趋化因子 10(CXCL10)介导招募炎症细胞,如单核细胞。因此,它可能在 COPD 中发挥关键作用。在这里,进行了一项病例对照研究,以评估 CXCL10 标签单核苷酸多态性与 COPD 风险之间的关联。根据 30 名健康对照者的连锁不平衡(LD)分析,确定了 4 个标签 SNP,包括 rs4256246、rs4508917、rs56061981 和 rs56316945。进一步在 480 例 COPD 病例和 488 例对照者中评估了这四个标签 SNP 与 COPD 风险之间的关系。我们发现,rs56061981 的“T”等位基因与降低 COPD 风险显著相关,而 rs56316945 的“G”等位基因与增加 COPD 风险显著相关。在调整性别、年龄、吸烟包年和生物质后,除隐性模型外,SNP rs56316945 在不同模型中均与增加 COPD 风险显著相关。在调整性别、年龄、吸烟包年和生物质后,除隐性模型外,SNP rs56061981 在不同模型中均与降低 COPD 风险显著相关。与 SNP 的吸烟状况和生物质分层分析支持 rs56061981 可能与生物质和吸烟相互作用从而调节 COPD 易感性,而 rs56216945 明显与 COPD 患者的肺功能严重程度相关。这项研究表明,CXCL10 基因启动子中的 rs56061981 和 rs56216945 与 COPD 的易感性有关。