Leptin receptor polymorphisms and lung function decline in COPD.
Leptin receptor polymorphisms and lung function decline in COPD.
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DOI：
10.1183/09031936.00120408
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发表时间：
2009-07
期刊：
影响因子：
--
通讯作者：
Barnes KC
中科院分区：
文献类型：
--
作者：
Hansel NN;Gao L;Rafaels NM;Mathias RA;Neptune ER;Tankersley C;Grant AV;Connett J;Beaty TH;Wise RA;Barnes KC
只有一小部分吸烟者会患上慢性阻塞性肺疾病（COPD），这表明遗传易感性在很大程度上起着作用。瘦素受体（LEPR）存在于人肺组织中，并可能在COPD发病机制中发挥作用。本研究探讨了慢性阻塞性肺病患者LEPR基因变异与肺功能下降之间的关系。从美国国家心肺血液研究所肺部健康研究中随机选择429名欧洲裔美国人，使用Illumina™GoldenGate平台（Broad Institute, Cambridge， MA， USA）对36个LEPR单核苷酸多态性（snp）进行基因分型。使用线性回归计算5年期间预测的强迫呼气量平均每年下降1.5%。线性回归模型也用于调整潜在的混杂因素。此外，用免疫组织化学方法评估了烟雾暴露的近交系小鼠肺中受体基因的体内表达。我们发现肺功能下降与21个snp之间存在显著关联（p<0.05）。单倍型分析证实了这些与个体标记的关联。近交系小鼠株的免疫组化结果支持LEPR在COPD发病机制中的潜在作用。我们发现LEPR基因的遗传变异与COPD吸烟者肺功能下降显著相关。我们的研究结果支持LEPR作为COPD新的候选基因的作用。
Only a fraction of all smokers develop chronic obstructive pulmonary disease (COPD), suggesting a large role for genetic susceptibility. The leptin receptor (LEPR) is present in human lung tissue and may play a role in COPD pathogenesis. The present study examined the association between genetic variants in the LEPR gene and lung function decline in COPD. In total, 429 European Americans were randomly selected from the National Heart Lung and Blood Institute Lung Health Study. 36 single nucleotide polymorphisms (SNPs) in LEPR were genotyped using the Illumina™ GoldenGate platform (Broad Institute, Cambridge, MA, USA). Mean annual decline in forced expiratory volume in 1 s % predicted over the 5-yr period was calculated using linear regression. Linear regression models were also used to adjust for potential confounders. In addition, in vivo expression of the receptor gene was assessed with immunohistochemistry on lungs from smoke-exposed inbred mice. We identified significant associations (p<0.05) between lung function decline and 21 SNPs. Haplotype analyses confirmed several of these associations seen with individual markers. Immunohistochemistry results in inbred mice strains support a potential role of LEPR in COPD pathogenesis. We identified genetic variants in the LEPR gene significantly associated with lung function decline in a population of smokers with COPD. Our results support a role for LEPR as a novel candidate gene for COPD.
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DOI：
10.1164/ajrccm.151.2.7842199
发表时间：
1995-02-01
影响因子：
24.7
作者：
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通讯作者：
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影响因子：
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DOI：
10.1164/ajrccm.162.4.9912016
发表时间：
2000-10-01
影响因子：
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作者：
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Schols, AMWJ
影响因子：
56.9
作者：
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影响因子：
10
作者：
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