CRP gene variation and risk of community-acquired pneumonia

  1. Kenneth J. MUKAMAL1,*,
  2. Jennifer K. PAI2,4,
  3. Ellen S. O'MEARA6,
  4. Russell P. TRACY9,
  5. Bruce M. PSATY7,8,
  6. Lewis H. KULLER10,
  7. Anne B. NEWMAN10,
  8. Sachin YENDE11,
  9. Gary C. CURHAN2,4,5,
  10. David S. SISCOVICK7,8,
  11. Eric B. RIMM2,3,4

Article first published online: 23 NOV 2009

DOI: 10.1111/j.1440-1843.2009.01661.x

Issue

Respirology

Respirology

Volume 15, Issue 1, pages 160–164, January 2010

Additional Information

How to Cite

MUKAMAL, K. J., PAI, J. K., O'MEARA, E. S., TRACY, R. P., PSATY, B. M., KULLER, L. H., NEWMAN, A. B., YENDE, S., CURHAN, G. C., SISCOVICK, D. S. and RIMM, E. B. (2010), CRP gene variation and risk of community-acquired pneumonia. Respirology, 15: 160–164. doi: 10.1111/j.1440-1843.2009.01661.x

Author Information

  1. 1

    Department of Medicine, Beth Israel Deaconess Medical Center, Departments of

  2. 2

    Epidemiology and

  3. 3

    Nutrition, Harvard School of Public Health,

  4. 4

    Channing Laboratory and

  5. 5

    Renal Division, Department of Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, Departments of

  6. 6

    Biostatistics,

  7. 7

    Epidemiology and

  8. 8

    Medicine, University of Washington, Seattle, WA,

  9. 9

    Department of Pathology, College of Medicine, University of Vermont, Burlington, VT, Departments of

  10. 10

    Epidemiology and

  11. 11

    Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA

*Kenneth J. Mukamal, Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, RO-114, Boston, MA 02215, USA. Fax: (617) 667-2854. Email: kmukamal@bidmc.harvard.edu

Publication History

  1. Issue published online: 27 DEC 2009
  2. Article first published online: 23 NOV 2009
  3. Received 16 March 2009; invited to revise 21 April 2009, 4 June 2009; revised 24 April 2009, 1 July 2009; accepted 30 July 2009 (Associate Editor: Yuben Moodley).

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Keywords:

  • C-reactive protein;
  • cohort study;
  • epidemiology;
  • pneumonia;
  • single nucleotide polymorphism

We tested whether variation in the CRP gene was associated with risk of pneumonia. We found that some genetic variants in CRP may be associated with risk of pneumonia, but not consistently in the manner expected from circulating CRP levels.

ABSTRACT

Background and objective:  CRP has several potentially antibacterial effects, and variation in the CRP gene is known to influence CRP levels. Whether this variation influences risk of infection, and hence whether CRP has anti-infective activity in humans, is uncertain.

Methods:  We evaluated a series of haplotype-tagging single nucleotide polymorphisms among 5374 individuals in the Cardiovascular Health Study, a cohort of older adults from four communities, who were followed for community-acquired pneumonia for 12–13 years. Secondarily, we evaluated whether these polymorphisms varied among men in the Health Professionals Follow-up Study who self-reported pneumonia on biennial questionnaires.

Results:  There were 581 (507 white and 74 black) Cardiovascular Health Study participants with incident hospitalizations for pneumonia. No single nucleotide polymorphism or haplotypes were associated with risk among white Cardiovascular Health Study participants. Among black participants, the haplotype tagged by A790T was associated with lower risk of incident pneumonia (hazard ratio 0.5; 95% confidence interval: 0.3–0.9) and with higher CRP levels. In Health Professionals Follow-up Study, a separate haplotype was associated with less frequent self-reported pneumonia but not with circulating CRP levels.

Conclusions:  Some genetic variants in CRP may be associated with risk of pneumonia, but haplotypes associated with risk are variably associated with baseline CRP levels. If CRP is a relevant component of innate immunity in humans, the inducibility or tissue-specificity of expression may be at least as important as chronic circulating levels.

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