Title | CRP gene variation and risk of community-acquired pneumonia. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | Mukamal, KJ, Pai, JK, O'Meara, ES, Tracy, RP, Psaty, BM, Kuller, LH, Newman, AB, Yende, S, Curhan, GC, Siscovick, DS, Rimm, EB |
Journal | Respirology |
Volume | 15 |
Issue | 1 |
Pagination | 160-4 |
Date Published | 2010 Jan |
ISSN | 1440-1843 |
Keywords | African Americans, Aged, Aged, 80 and over, Body Mass Index, C-Reactive Protein, Cohort Studies, Community-Acquired Infections, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Haplotypes, Humans, Male, Pneumonia, Polymorphism, Single Nucleotide, Prospective Studies, Risk Factors, Smoking |
Abstract | <p><b>BACKGROUND AND OBJECTIVE: </b>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.</p><p><b>METHODS: </b>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.</p><p><b>RESULTS: </b>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.</p><p><b>CONCLUSIONS: </b>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.</p> |
DOI | 10.1111/j.1440-1843.2009.01661.x |
Alternate Journal | Respirology |
PubMed ID | 19947988 |
PubMed Central ID | PMC2869386 |
Grant List | HL34594 / HL / NHLBI NIH HHS / United States N01 HC085086 / HC / NHLBI NIH HHS / United States U01 HL080295-04 / HL / NHLBI NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States N01 HC075150 / HC / NHLBI NIH HHS / United States P01 CA055075 / CA / NCI NIH HHS / United States N01 HC015103 / HC / NHLBI NIH HHS / United States U01 HL080295-01 / HL / NHLBI NIH HHS / United States R01 HL035464-22 / HL / NHLBI NIH HHS / United States CA55075 / CA / NCI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States R01 HL034594-25 / HL / NHLBI NIH HHS / United States N01-HC-85086 / HC / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States N01 HC-55222 / HC / NHLBI NIH HHS / United States N01 HC055222 / HC / NHLBI NIH HHS / United States P01 CA055075-14 / CA / NCI NIH HHS / United States R01 HL034594 / HL / NHLBI NIH HHS / United States N01-HC-75150 / HC / NHLBI NIH HHS / United States R01 HL071862 / HL / NHLBI NIH HHS / United States HL71862 / HL / NHLBI NIH HHS / United States HL35464 / HL / NHLBI NIH HHS / United States N01HC75150 / HL / NHLBI NIH HHS / United States R01 HL035464 / HL / NHLBI NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States R01 HL071862-07 / HL / NHLBI NIH HHS / United States N01 HC045133 / HC / NHLBI NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States P01 CA055075-199003 / CA / NCI NIH HHS / United States |