Hedgehog-interacting protein is a COPD susceptibility gene: the Rotterdam Study
Hedgehog-interacting protein is a COPD susceptibility gene: the Rotterdam Study
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DOI：
10.1183/09031936.00129509
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发表时间：
2010-07-01
影响因子：
24.3
通讯作者：
Stricker, B. H. Ch.
中科院分区：
文献类型：
--
作者：
van Durme, Y. M. T. A.;Eijgelsheim, M.;Stricker, B. H. Ch.
Hedgehog信号通路在肺形态发生和细胞对肺损伤的反应中起重要作用。一项全基因组关联研究表明，刺猬相互作用蛋白（Hip）基因附近的两个单核苷酸多态性（SNP），SNP标识符rs 1828591和rs 13118928，与慢性阻塞性肺疾病（COPD）的风险相关。本研究的目的是验证髋关节基因附近的遗传变异与COPD之间的关联，并调查吸烟行为是否会改变风险估计，鹿特丹研究通过logistic回归分析对髋关节基因SNPs与COPD之间的关联进行了研究，并对几个协变量进行了调整。此外，还进行了一项关联Meta分析，包括来自COPD全基因组关联研究的数据，两种SNP均与COPD风险显著相关（OR 0.80; 95%CI 0.72-0.91）。次要G等位基因纯合性导致COPD风险降低约40%（95%CI 0.47- 0.78）。有一个显着的相互作用与吸烟包年数（p=0.004）。Meta分析得出，每增加一个G等位基因，COPD的优势比为0.80（p=3.4x10（-9））。Hip基因附近的遗传变异与COPD的风险显著相关，这取决于吸烟包年数。
The Hedgehog signalling pathway plays an important role in lung morphogenesis and cellular responses to lung injury. A genome- wide association study has demonstrated that two single nucleotide polymorphisms (SNPs) near the Hedgehog- interacting protein (Hip) gene, SNP identifiers rs1828591 and rs13118928, are associated with risk of chronic obstructive pulmonary disease (COPD). The aim of the present study was to validate the observed association between genetic variation near the Hip gene and COPD, and to investigate whether risk estimates were modified by smoking behaviour.The association between the Hip gene SNPs and COPD was investigated in the Rotterdam Study by logistic regression analyses, adjusted for several covariates. In addition, an association meta- analysis was performed that included data from the genome-wide association study on COPD.Both SNPs were significantly associated with risk of COPD (OR 0.80; 95% CI 0.72-0.91). Homozygosity for the minor G allele resulted in a decreased risk of COPD of similar to 40% (95% CI 0.47-.78). There was a significant interaction with the number of pack-years of smoking (p=0.004). The meta- analysis yielded an odds ratio for COPD of 0.80 per additional G allele (p=3.4x10(-9)).Genetic variation near the Hip gene was significantly associated with risk of COPD, depending on the number of pack-years of smoking.