CRP gene variation and risk of community-acquired pneumonia.
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.
Mukamal
Kenneth J
KJ
Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. kmukamal@bidmc.harvard.edu
Pai
Jennifer K
JK
O'Meara
Ellen S
ES
Tracy
Russell P
RP
Psaty
Bruce M
BM
Kuller
Lewis H
LH
Newman
Anne B
AB
Yende
Sachin
S
Curhan
Gary C
GC
Siscovick
David S
DS
Rimm
Eric B
EB
D001741:Black or African American / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000235:genetics*; D015331:Cohort Studies; D017714:Community-Acquired Infections / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D011014:Pneumonia / Q000235:genetics* / Q000382:microbiology*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D044465:White People / Q000235:genetics
D002097:C-Reactive Protein