C-reactive protein levels, haplotypes, and the risk of incident chronic obstructive pulmonary disease.
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is characterized by substantial chronic inflammation in the pulmonary compartment as well as in the systemic circulation.


OBJECTIVE
To investigate potentially causal association, we examined whether serum levels of high-sensitivity C-reactive protein (hsCRP) and variations in the CRP gene are associated with the risk of developing COPD.


METHODS
This study is part of the Rotterdam Study, a prospective population-based cohort study among subjects aged 55 years or older. At baseline, 6,836 subjects without COPD had a blood sample available for assessment of hsCRP serum levels and haplotypes of the CRP gene. We analyzed the association between hsCRP levels, CRP gene haplotypes, and incident COPD with Cox proportional hazard models, adjusted for age, sex, and other confounders.


RESULTS
High levels of hsCRP (>3 mg/L) were associated with a significantly increased risk of incident COPD (hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.16-2.49) compared with persons with low levels (<1 mg/L). The risk remained increased after adjusting for potential confounders and introducing a latency period of 3 years. The risk was most pronounced in former smokers (HR, 2.2; 95% CI, 1.12-3.74). hsCRP was not a risk factor in never smokers. No CRP single nucleotide polymorphism or haplotype was associated with a significantly increased or decreased COPD risk.


CONCLUSIONS
Increased hsCRP levels are predictive for the occurrence of COPD in smokers. However, haplotypes of the CRP gene, which influence hsCRP levels, are not associated with an altered risk of developing COPD.
van Durme
Yannick M T A
YM
Department of Respiratory Medicine, Ghent University and Ghent University Hospital, Ghent, Belgium.
Verhamme
Katia M C
KM
Aarnoudse
Albert-Jan L H J
AJ
Van Pottelberge
Geert R
GR
Hofman
Albert
A
Witteman
Jacqueline C M
JC
Joos
Guy F
GF
Brusselle
Guy G
GG
Stricker
Bruno H C
BH
D000368:Aged; D000369:Aged, 80 and over; D002097:C-Reactive Protein / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D012307:Risk Factors
D002097:C-Reactive Protein