Systemic CRP (C-reactive protein) has been associated with impaired lung function. A causal relationship would increase the value of CRP as both a diagnostic and therapeutic tool. We assessed the association between lung function parameters, circulating CRP and CRP polymorphisms using Mendelian randomization in efforts to attribute causality to known associations. Spirometric parameters of FEV1 (forced expiratory volume in 1 s) and FVC (forced vital capacity) were determined in 2173 men participating in the Caerphilly Prospective Study. Lung function measures on 1021 participants were available at follow-up (mean, 16.8 years later). Serum CRP levels were measured at baseline, and three CRP polymorphisms were analysed. Haplotype analysis was performed. Serum CRP levels at baseline were inversely associated with contemporaneous FEV1 and FVC as well as at follow-up (P<0.001) even after adjustment for conventional confounders. Serum CRP was associated with FEV1 decline (P=0.04). All three CRP polymorphisms (rs1800947, rs1130864 and rs1205) predicted serum CRP; however, there were no clear associations of the polymorphisms or haplotypes with lung function or with lung function decline. In conclusion, serum CRP was associated with lung function cross-sectionally; however, CRP polymorphisms were not associated with lung function or decline, suggesting that the CRP–lung function relationship is due to reverse causality, an unmeasured confounding factor or only has a modest causal effect.
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Research Article|
December 22 2010
The CRP genotype, serum levels and lung function in men: the Caerphilly Prospective Study
Charlotte E. Bolton;
*Wales Heart Research Institute, School of Medicine, Cardiff University, Heath Park, Cardiff, Wales, U.K.
†Nottingham Respiratory Biomedical Research Unit, University of Nottingham, City Hospital, Hucknall Road, Nottingham, U.K.
Correspondence: Dr Charlotte E. Bolton (email [email protected]).
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Wiebke Schumacher;
Wiebke Schumacher
‡Department of Social Medicine, University of Bristol, Canynge Hall, Whiteladies Road, Bristol, U.K.
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John R. Cockcroft;
John R. Cockcroft
*Wales Heart Research Institute, School of Medicine, Cardiff University, Heath Park, Cardiff, Wales, U.K.
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Nicholas J. Timpson;
Nicholas J. Timpson
§MRC CAiTE Centre, Department of Social Medicine, University of Bristol, Canynge Hall, Whiteladies Road, Bristol, U.K.
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George Davey Smith;
George Davey Smith
‡Department of Social Medicine, University of Bristol, Canynge Hall, Whiteladies Road, Bristol, U.K.
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John Gallacher;
John Gallacher
∥Department of Epidemiology, Statistics and Public Health, Cardiff University, Cardiff, Wales, U.K.
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Anne Rumley;
Anne Rumley
¶University Department of Medicine, Glasgow Royal Infirmary, Glasgow, U.K.
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Gordon D. Lowe;
Gordon D. Lowe
¶University Department of Medicine, Glasgow Royal Infirmary, Glasgow, U.K.
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Shah Ebrahim;
Shah Ebrahim
**London School of Hygiene and Tropical Medicine, University of London, London, U.K.
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Dennis J. Shale;
Dennis J. Shale
*Wales Heart Research Institute, School of Medicine, Cardiff University, Heath Park, Cardiff, Wales, U.K.
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Yoav Ben-Shlomo
Yoav Ben-Shlomo
‡Department of Social Medicine, University of Bristol, Canynge Hall, Whiteladies Road, Bristol, U.K.
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Publisher: Portland Press Ltd
Received:
October 08 2010
Revision Received:
November 10 2010
Accepted:
November 16 2010
Accepted Manuscript online:
November 16 2010
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2011 Biochemical Society
2011
Clin Sci (Lond) (2011) 120 (8): 347–355.
Article history
Received:
October 08 2010
Revision Received:
November 10 2010
Accepted:
November 16 2010
Accepted Manuscript online:
November 16 2010
Citation
Charlotte E. Bolton, Wiebke Schumacher, John R. Cockcroft, Nicholas J. Timpson, George Davey Smith, John Gallacher, Anne Rumley, Gordon D. Lowe, Shah Ebrahim, Dennis J. Shale, Yoav Ben-Shlomo; The CRP genotype, serum levels and lung function in men: the Caerphilly Prospective Study. Clin Sci (Lond) 1 April 2011; 120 (8): 347–355. doi: https://doi.org/10.1042/CS20100504
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