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9thÂ慢性阻塞性肺病与肺部国际会议- FAM13A和IREB2基因变异与中国农村人群慢性阻塞性肺病易感性相关:一项病例对照研究

摘要

全基因组关联研究确定了几个与慢性阻塞性肺疾病(COPD)风险相关的基因组区域，包括4q22和15q25区域。这些区域包含FAM13A和IREB2基因，这些基因与COPD相关，但缺乏中国患者的数据。本研究的目的是鉴定与中国西北地区COPD相关的FAM13A和IREB2的新遗传变异。这是一项2014年1月至2016年12月在宁夏回族自治区进行的病例对照研究。患者根据FEV1/FVC(70%)分组为COPD和对照组。利用Agena MassARRAY平台对FAM13A和IREB2基因中的7个标记单核苷酸多态性(SNPs)进行基因分型。使用逻辑回归来确定snp和copdisk之间的关系。FAM13A中Rs17014601与COPD在加性模型(优势比[OR]=1.36, 95%可信区间[CI]:1.11? 1.67, P=0.003)、杂合子模型(OR=1.76, 95% CI:1.33? 2.32, P=0.0001)和显性模型(OR=1.67, 95% CI:1.28? 2.18, P=0.0001)中显著相关。分层分析表明，从不吸烟的人患病风险更高。irbb2中的rs16969858与COPD显著相关，但仅在单因素分析中，多因素分析未显示任何相关性。结果表明，FAM13A基因中的新变异rs17014601与中国农村人群的COPD风险显著相关。需要进一步的研究来证实该变异在COPD发展和进展中的作用。 Chronic obstructive pulmonary disease (COPD) could be a major explanation for morbidity and mortality worldwide. it's characterized by persistent respiratory symptoms and limitation of air flow.1 within the People's Republic of China, the prevalence of COPD in individuals of $ 40 years old is estimated at 8.2% 2 or varies from 5% to 13% in several provinces. / cities.3 Cigarette smoking is taken into account the foremost important risk factor, but genetic characteristics play a crucial role in susceptibility to COPD. Genome-wide association studies (GWAS) identified several genomic regions related to an increased risk of COPD. Some GWAS loci are found on the FAM13A gene on chromosome 4q22 and at the 15q25 locus, which has the IREB2 gene. Considered to be an indication transduction gene because of the RhoGAP functional domain within the exon region, 9 but it's now known to be related to signaling of β-catenin, which is generally activated during injury repair and tissue regeneration10, eleven. Hypoxia often accompanies COPD and improves FAM13A expression.9 Furthermore; Kim et al12 showed that FAM13A SNPs related to an increased risk of COPD were also related to an increased expression of FAM13A within the lungs, suggesting a possible causal association with pathological changes within the lung. Corvol et al13 showed that the association of the FAM13A gene with lung function parameters (FEV1% predicted and FEV1 / FVC) was observed in several independent cohorts, suggesting that FAM13A is related to a selected COPD phenotype. Furthermore, Choo ET al14 demonstrated an association between the CTGA diploma in FAM13A and therefore the emphysema phenotype of COPD, and Jiang et al11 provided the premise for the role of FAM13A within the development of emphysema. A recent study by Corvol ET al15 showed that FAM13A and therefore the epithelial-mesenchymal transition (EMT) of the airways are closely associated with fibrocystic disease of the pancreas. EMT is additionally believed to play a crucial role in airway remodeling in COPD.16 Taken together, these results suggest that FAM13A is involved within the etiology of lung disease and COPD, iron is found in smoke. cigarette smoking17 and has been shown to disrupt lung homeostasis, making lung tissues more liable to damage from any cause.18 IREB2 could be a gene that ends up in iron regulatory protein 2 (IRP2), which plays a task in key role in iron homeostasis. IREB2 is in an exceedingly strong linkage disequilibrium with the nicotine receptor genes (CHRNA3 and 5) .5 Expression of IREB2 increases within the lungs of COPD patients.19 IRP2 regulates cellular iron homeostasis and mitochondrial function.20, 21 Some variants of IREB2 are reported to affect COPD within the presence of high levels of iron because of exposure to cigarette smoke.18 Therefore, there can be some association between IREB2 and respiratory conditions like COPD. Jin ZhangÂ

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