TY - JOUR T1 - CRP gene variation and risk of community-acquired pneumonia. JF - Respirology Y1 - 2010 A1 - Mukamal, Kenneth J A1 - Pai, Jennifer K A1 - O'Meara, Ellen S A1 - Tracy, Russell P A1 - Psaty, Bruce M A1 - Kuller, Lewis H A1 - Newman, Anne B A1 - Yende, Sachin A1 - Curhan, Gary C A1 - Siscovick, David S A1 - Rimm, Eric B KW - African Americans KW - Aged KW - Aged, 80 and over KW - Body Mass Index KW - C-Reactive Protein KW - Cohort Studies KW - Community-Acquired Infections KW - European Continental Ancestry Group KW - Female KW - Genetic Predisposition to Disease KW - Haplotypes KW - Humans KW - Male KW - Pneumonia KW - Polymorphism, Single Nucleotide KW - Prospective Studies KW - Risk Factors KW - Smoking AB -

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.

VL - 15 IS - 1 U1 - http://www.ncbi.nlm.nih.gov/pubmed/19947988?dopt=Abstract ER -