Association of TRPV4 gene polymorphisms with chronic obstructive pulmonary disease.
Association of TRPV4 gene polymorphisms with chronic obstructive pulmonary disease.
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DOI：
10.1093/hmg/ddp111
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发表时间：
2009-06
影响因子：
3.5
通讯作者：
G. Zhu;A. Gulsvik;P. Bakke;S. Ghatta;W. Anderson;D. Lomas;E. Silverman;S. Pillai
中科院分区：
文献类型：
--
作者：
G. Zhu;A. Gulsvik;P. Bakke;S. Ghatta;W. Anderson;D. Lomas;E. Silverman;S. Pillai
慢性阻塞性肺疾病（COPD）以气道上皮损伤、支气管收缩、实质破坏和粘液高分泌为特征。瞬时受体电位香草酸4（TRPV 4）在被广泛的刺激激活后，起控制气道上皮细胞体积和上皮及内皮通透性的作用;它还触发支气管平滑肌收缩并参与粘液纤毛转运的自动调节。TRPV 4的这些功能可能在COPD发病机制的调控中起重要作用，因此TRPV 4是COPD的候选基因。我们对TRPV 4的20个单核苷酸多态性（SNPs）进行了基因分型，并在两个独立的大型人群中检测了定性COPD和定量FEV（1）和FEV（1）/（F）VC表型。该家系共606个家系，包括1891名个体，病例对照样本包括953名COPD病例和956名对照。对家庭数据进行了基于家庭的关联检验。在病例对照数据中使用Logistic回归和线性模型来复制关联结果。在家族数据中，20个SNPs中有7个与COPD相关（2.5 x 10（-4）<或= P <或= 0.04），6个SNPs与FEV（1）/VC相关（0.02 <或= P <或= 0.03）。7个与COPD相关的SNPs中有4个在病例对照人群中表现出相同效应方向的重复关联（0.02 <或= P <或= 0.03）。显著的单倍型关联支持单SNP分析的结果。因此，TRPV 4基因的多态性与COPD相关。
Chronic obstructive pulmonary disease (COPD) is characterized by airway epithelial damage, bronchoconstriction, parenchymal destruction and mucus hypersecretion. Upon activation by a broad range of stimuli, transient receptor potential vanilloid 4 (TRPV4) functions to control airway epithelial cell volume and epithelial and endothelial permeability; it also triggers bronchial smooth muscle contraction and participates in autoregulation of mucociliary transport. These functions of TRPV4 may be important for the regulation of COPD pathogenesis, so TRPV4 is a candidate gene for COPD. We genotyped 20 single nucleotide polymorphisms (SNPs) in TRPV4, and tested qualitative COPD and quantitative FEV(1) and FEV(1)/(F)VC phenotypes in two independent large populations. The family population had 606 pedigrees including 1891 individuals, and the case-control sample included 953 COPD cases and 956 controls. Family-based association tests were performed in the family data. Logistic regression and linear models were used in the case-control data to replicate the association results. In the family data, seven out of 20 SNPs tested were associated with COPD (2.5 x 10(-4) < or = P < or = 0.04) and six SNPs were associated with FEV(1)/VC (0.02 < or = P < or = 0.03) from family-based association tests (PBAT) analysis. Four out of the seven SNPs associated with COPD demonstrated replicated associations with the same effect directions in the case-control population (0.02 < or = P < or = 0.03). Significant haplotype associations supported the results of single SNP analyses. Thus, polymorphisms in the TRPV4 gene are associated with COPD.