一项纵向研究中的基因易感性鉴定证实了慢性阻塞性肺疾病发展中的新基因座，并影响肺功能下降。
Gene susceptibility identification in a longitudinal study confirms new loci in the development of chronic obstructive pulmonary disease and influences lung function decline.
作者信息
Xie Jungang, Wu Hongxu, Xu Yuzhu, Wu Xiaojie, Liu Xue, Shang Jin, Zhao Jianping, Zhao Junling, Wang Jianmiao, Dela Cruz Charles S, Xiong Weining, Xu Yongjian
机构信息
Department of Respiratory and Critical Care Medicine, Tongji hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Section of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, USA.
出版信息
Respir Res. 2015 Apr 18;16(1):49. doi: 10.1186/s12931-015-0209-3.
BACKGROUND
To identify COPD associated gene susceptibility and lung function in a longitudinal cohort including COPD and subjects who were at risk for developing COPD, and to replicate this in two cross-sectional and longitudinal populations in Chinese Han population.
METHODS
Three cohorts were recruited in this study, including an 18-year follow-up population (306 COPD and 743 control subjects) in one village in 1992 and it changed to 409 COPD and 611 controls in 2010, a 2 year follow-up study in another village (374 COPD and 377 controls) and another 2 year follow-up one in a city (541 COPD and 560 controls) in 2010. Sixteen candidate single nucleotide polymorphisms (SNPs) were selected for genotyping. Among them, 5SNPs in or near HHIP, 1SNP in IREB2 and 1SNP in FAM13A were previously reported to be associated with COPD susceptibility or lung function decline. And another 9SNPs were selected from HapMap website as HHIP tags. In 2010, totaling 1,324 COPD patients and 1,548 healthy controls were finally included in our genetic susceptibility analyses.
RESULTS
We identified two new regions showing an association with COPD susceptibility in the Human Hedgehog interacting protein (HHIP) rs11100865 and rs7654947, and we confirmed that the family with sequence similarity 13 member A gene (FAM13A) rs7671167 was associated with the development of COPD in Chinese Han population. And the HHIP rs7654947 and FAM13A rs7671167 were associated with lung function decline, and this result was replicated in other two populations.
CONCLUSIONS
These results suggest an important role of the HHIP and FAM13A regions as genetic risk factors for COPD development and lung function decline in Chinese Han population. Future research on these genes should focus on the molecular mechanisms of these genes on developing COPD and creating therapies to alleviate reduced lung function.
背景
在一个包含慢性阻塞性肺疾病（COPD）患者和有患COPD风险的受试者的纵向队列中，确定与COPD相关的基因易感性和肺功能，并在中国汉族人群的两个横断面和纵向人群中进行重复验证。
方法
本研究招募了三个队列，包括1992年在一个村庄进行的为期18年的随访人群（306例COPD患者和743例对照受试者），到2010年变为409例COPD患者和611例对照；2010年在另一个村庄进行的为期2年的随访研究（374例COPD患者和377例对照）以及在一个城市进行的另一个为期2年的随访研究（541例COPD患者和560例对照）。选择16个候选单核苷酸多态性（SNP）进行基因分型。其中，HHIP基因内或附近的5个SNP、IREB2基因中的1个SNP和FAM13A基因中的1个SNP先前已报道与COPD易感性或肺功能下降相关。另外9个SNP从HapMap网站作为HHIP标签选出。2010年，共有1324例COPD患者和1548例健康对照最终纳入我们的遗传易感性分析。
结果
我们在人刺猬相互作用蛋白（HHIP）的rs11100865和rs7654947中发现了两个与COPD易感性相关的新区域，并证实序列相似性家族13成员A基因（FAM13A）的rs7671167与中国汉族人群COPD的发生相关。并且HHIP的rs7654947和FAM13A的rs7671167与肺功能下降相关，这一结果在其他两个人群中得到了重复验证。
结论
这些结果表明，HHIP和FAM13A区域作为中国汉族人群COPD发生和肺功能下降的遗传危险因素具有重要作用。未来对这些基因的研究应聚焦于这些基因在COPD发生中的分子机制以及开发缓解肺功能降低的治疗方法。
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