Genetic determinants of C-reactive protein in chronic obstructive pulmonary disease

¹ Channing Laboratory and Pulmonary/Critical Care Division
² Hematology Division, Dept of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA

^* To whom correspondence should be addressed. E-mail: craig.hersh{at}channing.harvard.edu.

	Abstract

Chronic obstructive pulmonary disease (COPD) is associated with a systemic inflammatory state, marked by elevations in serum inflammatory markers, including C-reactive protein (CRP). We sought to determine predictors of CRP levels, to estimate the genetic influence on CRP levels, and to identify genetic variants that affect CRP in a family-based study of COPD.

CRP was measured by a high-sensitivity assay in participants from the Boston Early-Onset COPD Study. Predictors of CRP level were determined using multilevel linear models. Variance component analysis was used to estimate heritability and to perform genome-wide linkage analysis for CRP levels. Two variants in surfactant protein B (SFTPB) were tested for association with CRP level.

Increased age, female sex, higher body mass index, greater pack-years of smoking and reduced forced expiratory volume in 1 second were all associated with increased CRP levels. There was a significant genetic influence on CRP (heritability = 0.25, p=0.00001). Genome-wide linkage analysis revealed several potentially interesting chromosomal regions, though no significant evidence for linkage was found. A short tandem repeat marker near SFTPB was significantly associated with CRP levels (p=0.007).

There is a genetic influence on CRP levels in COPD patients. Preliminary evidence suggests an association of SFTPB with systemic inflammation in COPD.

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