HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplementary table All Versions of this Article: 34/3/598    most recent 09031936.00141808v1 Alert me when this article is cited Alert me if a correction is posted Permissions Request Permissions Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Zhu, G. PubMed PubMed Citation Articles by Zhu, G.

CTLA4 gene polymorphisms are associated with chronic bronchitis

¹ Genetics, GlaxoSmithKline, Research and Development, Research Triangle Park, NC, ⁸ Brigham and Women's Hospital, Boston, MA, USA. ² Hospital Universitario Son Dureta, Palma de Mallorca, ³ Fundación Caubet-Cimera, Bunyola, Mallorca, ⁴ Institut del Tòrax, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain. ⁵ University of Bergen, Bergen, Norway. ⁶ University of British Columbia, Vancouver, BC, Canada. ⁷ Cambridge Institute for Medical Research, Cambridge, UK. ⁹ A list of the ICGN investigators is given in the Acknowledgements section.

CORRESPONDENCE: S. G. Pillai, Glaxo SmithKline R&D, 5 Moore Drive, Research Triangle Park, NC 27709, USA. E-mail: pillaisreekumar{at}yahoo.com

Keywords: Chronic bronchitis, chronic obstructive pulmonary disease, genetic association, replication, smoking, tobacco

Received: September 15, 2008
Accepted April 7, 2009

Chronic obstructive pulmonary disease (COPD) is characterised by chronic and progressive dyspnoea, cough and sputum production. T-lymphocytes may play a key role in the pathogenesis of COPD and chronic bronchitis. Cytotoxic T-lymphocyte antigen (CTLA) 4 is a potential candidate gene because it modulates T-cell activation.

Genetic association between nine CTLA4 single nucleotide polymorphisms (SNPs) and chronic bronchitis was assessed in 606 pedigrees (1,896 individuals) from the International COPD Genetics Network (ICGN) population. We then replicated the associations in 342 COPD subjects with chronic bronchitis and 511 COPD subjects without chronic bronchitis from Bergen, Norway. Family-based association tests were used to analyse the ICGN cohort, and a logistic regression model was used for the Bergen cohort.

Six CTLA4 SNPs were significantly associated with chronic bronchitis in the ICGN cohort (0.0079p0.0432), with three being replicated with the same directionality of association in the Bergen cohort (0.0325p0.0408). One of these replicated SNPs (rs231775) encodes the Thr to Ala substitution at amino acid position 17. Haplotype analyses supported the results of single SNP analyses.

Thus, CTLA4 is likely to be a genetic determinant of chronic bronchitis among COPD cases.