Association of the hCLCA1 gene with childhood and adult asthma

Abstract

Asthma is caused by bronchial inflammation. This inflammation involves mucus overproduction and hypersecretion. Recently, a mouse model of asthma showed that gob-5 is involved in the pathogenesis of asthma. The gob-5 gene is involved in mucus secretion and its expression is upregulated upon antigen attack in sensitized mice. The observation suggests that human homologue of gob-5, hCLCA1 (human calcium-dependent chloride channel-1), may be involved in human disease. We screened for single-nucleotide polymorphisms (SNPs) in hCLCA1 in the Japanese population. We identified eight SNPs, and performed association studies using 384 child patients with asthma, 480 adult patients with asthma, and 672 controls. In haplotype analysis, we found a different haplotype distribution pattern between controls and childhood asthma (Po0.0001) and between controls and adult asthma (P ¼ 0.0031). We identified a high-risk haplotype (CATCAAGT haplotype; P ¼ 0.0014) and a low-risk haplotype (TGCCAAGT haplotype; P ¼ 0.00010) in cases of childhood asthma. In diplotype analysis, patients who had the CATCAAGT haplotype showed a higher risk for childhood asthma than those who did not (P ¼ 0.0011). Individuals who had the TGCCAAGT haplotype showed a lower risk for childhood asthma than those who did not (Po0.0001). Our data suggested that variation of the hCLCA1 gene affects patients' susceptibility for asthma.

Gene expression analysis in a murine model of allergic asthma reveals overlapping disease and therapy dependent pathways in the lung

“…TFF2 and CLCA3/Gob-5, expressed by epithelial cells and associated with the presence of goblet cells and mucus production, were recently implicated in preclinical lung inflammation models and in genetic studies of human asthma. 18,19 However, the induction of other mucus associated genes including AGR2/ Gob-4, RegIII gamma and FCGBP, following IL-13 administration and their dependence on IL-13 and STAT6 signaling have not been previously reported.…”

Genomic, Tissue Expression, and Protein Characterization of pCLCA1, a Putative Modulator of Cystic Fibrosis in the Pig

“…In contrast, antibody p1-C-1a raised against the predicted carboxy-terminal fragment failed to detect any specific protein in transfected cells or tissue lysates (data not shown), although it yielded staining patterns identical to those of antibodies p1-N-1a and p1-N-2a in the immunohistochemical experiments (see below). The sequence of the pCLCA1 clone used for transfection of the cells was identical to the sequence obtained from the respective BAC clones, but was two amino acids shorter than the published sequence (GenBank accession number NP_999313), which might be due to allelic variations, as described for other CLCA homologs (Kamada et al 2004;Anton et al 2005). …”

“…Second, the human hCLCA3 is thought to represent a pseudogene, whereas its murine and bovine orthologs are not (Elble et al 1997;Gruber and Pauli 1999). Third, distinct allelic variations that appear to be species-specific have been reported for the human hCLCA1 (Kamada et al 2004) and the equine eCLCA1 (Anton et al 2005). Fourth, the murine mCLCA6 protein is expressed in different cell types and in different subcellular structures than its direct human ortholog, hCLCA4 (Bothe et al 2008).…”

An association study of asthma and related phenotypes with polymorphisms in negative regulator molecules of the TLR signaling pathway

“…Improvement in their FEV 1 measurement was at least 12% in childhood asthma and 20% in adult asthma after b 2 -agonist inhalation (National Heart, Lung, and Blood Institute 1991;Hasegawa et al 2004;Kamada et al 2004). Diagnosis of atopic asthma was based on one or more positive skinscratch-test responses to a range of seven common aeroallergens in the presence of a positive histamine control and a negative vehicle control.…”

“…The sequences were analyzed and polymorphisms identified using SEQUENCHER software (Gene Codes Corporation, Ann Arbor, MI, USA). Genotyping of polymorphisms was performed by using the Invader assay or the TaqMan allele-specific amplification (TaqMan-ASA) method or PCR restriction fragment length polymorphism (PCR-RFLP) analysis as described Kamada et al 2004). For the À1464A>G, 21927A>T, 22149G>A, 48837A>G, and 54406C>T polymorphisms in IRAK-M, genotyping was performed by the Invader method (Ohnishi et al 2001).…”