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Associations of IL6 polymorphisms with lung function decline and COPD
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  1. J-Q He1,
  2. M G Foreman2,
  3. K Shumansky1,
  4. X Zhang1,
  5. L Akhabir1,
  6. D D Sin1,
  7. S F P Man1,
  8. D L DeMeo2,3,
  9. A A Litonjua2,3,
  10. E K Silverman2,3,
  11. J E Connett4,
  12. N R Anthonisen5,
  13. R A Wise6,
  14. P D Paré1,
  15. A J Sandford1
  1. 1The James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research and the Department of Medicine, St Paul’s Hospital, University of British Columbia, Vancouver, British Columbia, Canada
  2. 2Channing Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
  3. 3Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
  4. 4Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA
  5. 5Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
  6. 6Faculty of Medicine, Johns Hopkins University, Baltimore, Maryland, USA
  1. Dr A J Sandford, UBC James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, St Paul’s Hospital, 1081 Burrard Street, Vancouver, BC, Canada V6Z 1Y6; asandford{at}mrl.ubc.ca

Abstract

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

Methods: Seven and five 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 1 s (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 nine IL6 SNPs was genotyped in 389 cases of COPD 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 decline in FEV1 (0.023⩽p⩽0.041 in additive models). Among them, the IL6_-174C allele was associated with a rapid decline in 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: The results suggest that the IL6_-174G/C SNP is associated with a rapid decline in FEV1 and susceptibility to COPD in smokers.

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Supplementary materials

Footnotes

  • Competing interests: None.

  • Funding: This work was supported by grants from the Canadian Institutes of Health Research and National Institutes of Heath Grant 5R01HL064068-04. The Lung Health Study was supported by contract N01-HR-46002 from the Division of Lung Diseases of the National Heart, Lung, and Blood Institute. The NETT Genetics Ancillary Study was supported by National Institutes of Health grants HL075478 and HL71393. The Normative Aging Study is supported by the Cooperative Studies Program/ERIC of the US Department of Veterans Affairs and is a component of the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC). J-QH is the recipient of a Michael Smith Foundation for Health Research Fellowship and Izaak Walton Killam Memorial Scholarship Award. MGF was supported by HL007427. DLD was supported by HL072918. AJS is the recipient of a Canada Research Chair in genetics and a Michael Smith Foundation for Health Research Senior Scholar Award.

  • ▸ Additional information is published online only at http://thorax.bmj.com/content/vol64/issue8

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