CTLA4 gene polymorphisms are associated with chronic bronchitis

G. Zhu, A. Agusti, A. Gulsvik, P. Bakke, H. Coxsone, D. A. Lomas, E. K. Silverman, S. G. Pillai, P. M.A. Calverley, C. F. Donner, R. D. Levy, P. D. Paré, B. J. Make, S. I. Rennard, J. Vestbo, E. F.M. Wouters

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

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 (0.0079≤p≤0.0432), with three being replicated with the same directionality of association in the Bergen cohort (0.0325≤p≤0.0408). 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. Copyright

Original languageEnglish (US)
Pages (from-to)598-604
Number of pages7
JournalEuropean Respiratory Journal
Volume34
Issue number3
DOIs
StatePublished - Sep 1 2009
Externally publishedYes

Keywords

  • Chronic bronchitis
  • Chronic obstructive pulmonary disease
  • Genetic association
  • Replication
  • Smoking
  • Tobacco

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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    Zhu, G., Agusti, A., Gulsvik, A., Bakke, P., Coxsone, H., Lomas, D. A., Silverman, E. K., Pillai, S. G., Calverley, P. M. A., Donner, C. F., Levy, R. D., Paré, P. D., Make, B. J., Rennard, S. I., Vestbo, J., & Wouters, E. F. M. (2009). CTLA4 gene polymorphisms are associated with chronic bronchitis. European Respiratory Journal, 34(3), 598-604. https://doi.org/10.1183/09031936.00141808