title: Association of TRPV4 gene polymorphisms with chronic obstructive pulmonary disease.
abstract: 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.
authors.affiliation: Genetics, GlaxoSmithKline R&D, 5 Moore Drive, Research Triangle Park, NC 27709, USA.
authors.forename: Guohua
authors.initials: G
authors.lastname: Zhu
authors.forename: Amund
authors.initials: A
authors.lastname: Gulsvik
authors.forename: Per
authors.initials: P
authors.lastname: Bakke
authors.forename: Srinivas
authors.initials: S
authors.lastname: Ghatta
authors.forename: Wayne
authors.initials: W
authors.lastname: Anderson
authors.forename: David A
authors.initials: DA
authors.lastname: Lomas
authors.forename: Edwin K
authors.initials: EK
authors.lastname: Silverman
authors.forename: Sreekumar G
authors.initials: SG
authors.lastname: Pillai
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009664:Norway; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics*; D050916:TRPV Cation Channels / Q000235:genetics*
chemical_list: D050916:TRPV Cation Channels; C416986:TRPV4 protein, human