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Original article
C reactive protein and chronic obstructive pulmonary disease: a Mendelian randomisation approach
  1. Morten Dahl1,2,3,4,
  2. Jørgen Vestbo3,4,5,6,
  3. Jeppe Zacho1,2,3,4,
  4. Peter Lange3,4,5,
  5. Anne Tybjærg-Hansen2,3,4,7,
  6. Børge G Nordestgaard1,2,3,4
  1. 1Department of Clinical Biochemistry, Herlev Hospital, Copenhagen, Denmark
  2. 2The Copenhagen General Population Study, Herlev Hospital, Copenhagen, Denmark
  3. 3The Copenhagen City Heart Study, Bispebjerg Hospital, Copenhagen, Denmark
  4. 4Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
  5. 5Department of Cardiology and Respiratory Medicine, Hvidovre Hospital, Copenhagen, Denmark
  6. 6Respiratory Medicine Research Group, University of Manchester, Manchester, UK
  7. 7Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark
  1. Correspondence to Børge G Nordestgaard, Professor, Chief Physician, Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark; brno{at}heh.regionh.dk

Abstract

Background It is unclear whether elevated plasma C reactive protein (CRP) is causally related to chronic obstructive pulmonary disease (COPD). The authors tested the hypothesis that genetically elevated plasma CRP causes COPD using a Mendelian randomisation design.

Methods The authors measured high-sensitivity CRP in plasma, genotyped for four single nucleotide polymorphisms in the CRP gene, and screened for spirometry-defined COPD and hospitalisation due to COPD in 7974 individuals from the Copenhagen City Heart Study and in 32 652 individuals from the Copenhagen General Population Study.

Results Elevated plasma CRP >3 mg/l compared with <1 mg/l was associated with risk estimates of 1.8 and 2.8 for spirometry-based COPD and of 1.6 and 1.8 for hospitalisation due to COPD in the Copenhagen City Heart Study and the Copenhagen General Population Study, respectively. Genotype combinations of the four CRP polymorphisms were associated with up to a 62% increase in plasma CRP. However, these genotype combinations did not associate with increased risk of COPD or hospitalisation due to COPD in either cohort or in the two cohorts combined. On instrumental variable analysis, a doubling of plasma CRP versus a doubling of genetically elevated CRP resulted in ORs for COPD of 1.27 (95% CI 1.25 to 1.30) versus 1.01 (0.81 to 1.26) and for COPD hospitalisation of 1.47 (1.43 to 1.51) versus 0.82(0.59 to 1.13).

Conclusion Although elevated CRP is related to both a diagnosis of COPD and subsequent hospital admission, genetically elevated plasma CRP is not associated with an increased risk of clinical COPD. This suggests that the association between CRP levels and COPD is not causal.

  • COPD
  • genetics
  • CRP
  • biomarker
  • Mendelian randomisation
  • clinical epidemiology
  • COPD pathology
  • innate immunity
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Footnotes

  • Funding Danish Heart Foundation and Danish Lung Association.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of Herlev Hospital and Danish ethics committees.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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