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Associations of IL6 polymorphisms with lung function decline and COPD
  1. Jian-Qing He (jhe{at}mrl.ubc.ca)
  1. James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, University of British Columbia, Canada
    1. Marilyn G Foreman (marilyn.foreman{at}channing.harvard.edu)
    1. Channing Laboratory, United States
      1. Karey Shumansky (karey_shumansky{at}yahoo.com)
      1. James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, University of British Columbia, Canada
        1. Xuekui Zhang (xzhang{at}stat.ubc.ca)
        1. James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, University of British Columbia, Canada
          1. Loubna Akhabir (lakhabir{at}mrl.ubc.ca)
          1. James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, University of British Columbia, Canada
            1. Don D Sin (dsin{at}mrl.ubc.ca)
            1. James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, University of British Columbia, Canada
              1. S F Paul Man (pman{at}providencehealth.bc.ca)
              1. St Pauls' hospital, Vancouver, BC, Canada
                1. Dawn L Demeo (dawn.demeo{at}channing.harvard.edu)
                1. Channing Laboratory, United States
                  1. Augusto A Litonjua (augusto.litonjua{at}channing.harvard.edu)
                  1. Channing Laboratory, United States
                    1. Ed Silverman (ed.silverman{at}channing.harvard.edu)
                    1. Brigham and Women's Hospital, Boston, United States
                      1. John E Connett (john-c{at}ccbr.umn.edu)
                      1. University of Minnesota, United States
                        1. Nicholas R Anthonisen (anthonis{at}ms.umanitoba.ca)
                        1. University of Manitoba, Canada
                          1. Robert Wise (rwise{at}jhmi.edu)
                          1. Johns Hopkins University, United States
                            1. Peter Pare (ppare{at}mrl.ubc.ca)
                            1. James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, University of British Columbia, Canada
                              1. Andrew J Sandford (asandford{at}mrl.ubc.ca)
                              1. James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, University of British Columbia, Canada

                                Abstract

                                Background: Interleukin-6 (IL6) is a pleiotropic pro-inflammatory and immunomodulatory cytokine which likely plays an important role in the pathogenesis of COPD. There is a functional single nucleotide polymorphism (SNP), -174G/C, in the promoter region of IL6. We hypothesized that IL6 SNPs influence susceptibility for impaired lung function and COPD in smokers.

                                Methods: Seven and 5 SNPs in IL6 were genotyped in two nested case-control samples derived from the Lung Health Study (LHS) based on phenotypes of rate of decline of forced expiratory volume in one second (FEV1) over 5 years and baseline FEV1 at the beginning of the LHS. Serum IL6 concentrations were measured for all subjects. A partially overlapping panel of 9 IL6 SNPs was genotyped in 389 COPD cases from the National Emphysema Treatment Trial (NETT) and 420 controls from the Normative Aging Study (NAS).

                                Results: In the LHS, three IL6 SNPs were associated with FEV1 decline (0.023 ≤ P ≤ 0.041 in additive models). Among them the IL6_-174C allele was associated with rapid decline of lung function. The association was more significant in a genotype-based analysis (P = 0.006). In the NETT-NAS study, IL6_-174G/C and four other IL6 SNPs, all of which are in linkage disequilibrium with IL6_-174G/C, were associated with susceptibility to COPD (0.01 ≤ P ≤ 0.04 in additive genetic models).

                                Conclusion: Our results suggested that the IL6_-174G/C SNP is associated with rapid decline of FEV1 and susceptibility to COPD in smokers.

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