Gene susceptibility identification in a longitudinal study confirms new loci in the development of chronic obstructive pulmonary disease and influences lung function decline.
Gene susceptibility identification in a longitudinal study confirms new loci in the development of chronic obstructive pulmonary disease and influences lung function decline.
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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位点并影响肺功能下降
DOI：
10.1186/s12931-015-0209-3
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发表时间：
2015-04-18
影响因子：
5.8
通讯作者：
Xu Y
中科院分区：
文献类型：
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作者：
Xie J;Wu H;Xu Y;Wu X;Liu X;Shang J;Zhao J;Zhao J;Wang J;Dela Cruz CS;Xiong W;Xu Y
为了在包括COPD和有发生COPD风险的受试者的纵向队列中确定COPD相关基因易感性和肺功能，并在中国汉族人群的两个横向和纵向人群中重复这一点。包括18年的随访人群1992年，一个村庄的COPD受试者306人，对照受试者743人，2010年改为COPD 409人，对照611人，2010年在另一个村庄进行了为期2年的随访研究（374例COPD患者和377例对照患者），并在一个城市进行了为期2年的随访研究（541例COPD患者和560例对照患者）。选择16个候选单核苷酸多态性（SNPs）进行基因分型。其中5个位于HHIP或其附近的SNP、1个位于IREB 2的SNP和1个位于FAM 13 A的SNP与COPD易感性或肺功能下降相关。从HapMap网站上筛选出9个SNPs作为HHIP标签。在2010年，共有1,324名COPD患者和1,548名健康对照最终纳入我们的遗传易感性analysis.ResultsWe确定了两个新的区域显示与COPD易感性在人类刺猬相互作用蛋白（HHIP）rs 11100865和rs7654947，证实了序列相似的13成员A基因（FAM 13 A）rs7671167与中国汉族人群COPD的发生有关。HHIP rs7654947和FAM 13 A rs7671167与肺功能下降相关，这一结果在其他两个人群中也得到了证实。未来对这些基因的研究应该集中在这些基因发展COPD的分子机制上，并创造缓解肺功能下降的疗法。
BackgroundTo 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.MethodsThree 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.ResultsWe 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.ConclusionsThese 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.
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影响因子：
3.7
作者：
Lamontagne M;Couture C;Postma DS;Timens W;Sin DD;Paré PD;Hogg JC;Nickle D;Laviolette M;Bossé Y
通讯作者：
Bossé Y
影响因子：
--
作者：
Wilk, Jemma B.;Walter, Robert E.;Laramie, Jason M.;Gottlieb, Daniel J.;O'Connor, George T.
通讯作者：
O'Connor, George T.
影响因子：
30.8
作者：
Repapi, Emmanouela;Sayers, Ian;Tobin, Martin D.
通讯作者：
Tobin, Martin D.
影响因子：
24.3
作者：
van Durme, Y. M. T. A.;Eijgelsheim, M.;Stricker, B. H. Ch.
通讯作者：
Stricker, B. H. Ch.
影响因子：
30.8
作者：
通讯作者：
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