Genetic polymorphisms and the risk of stroke after cardiac surgery.
OBJECTIVE
Stroke represents a significant cause of morbidity and mortality after cardiac surgery. Although the risk of stroke varies according to both patient and procedural factors, the impact of genetic variants on stroke risk is not well understood. Therefore, we tested the hypothesis that specific genetic polymorphisms are associated with an increased risk of stroke after cardiac surgery.


METHODS
Patients undergoing cardiac surgery utilizing cardiopulmonary bypass surgery were studied. DNA was isolated from preoperative blood and analyzed for 26 different single-nucleotide polymorphisms. Multivariable logistic regression modeling was used to determine the association of clinical and genetic characteristics with stroke. Permutation analysis was used to adjust for multiple comparisons inherent in genetic association studies.


RESULTS
A total of 1635 patients experiencing 28 strokes (1.7%) were included in the final genetic model. The combination of the 2 minor alleles of C-reactive protein (CRP; 3'UTR 1846C/T) and interleukin-6 (IL-6; -174G/C) polymorphisms, occurring in 583 (35.7%) patients, was significantly associated with stroke (odds ratio, 3.3; 95% CI, 1.4 to 8.1; P=0.0023). In a multivariable logistic model adjusting for age, the CRP and IL-6 single-nucleotide polymorphism combination remained significantly associated with stroke (P=0.0020).


CONCLUSIONS
We demonstrate that common genetic variants of CRP (3'UTR 1846C/T) and IL-6 (-174G/C) are significantly associated with the risk of stroke after cardiac surgery, suggesting a pivotal role of inflammation in post-cardiac surgery stroke.
Grocott
Hilary P
HP
Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA. h.grocott@duke.edu
White
William D
WD
Morris
Richard W
RW
Podgoreanu
Mihai V
MV
Mathew
Joseph P
JP
Nielsen
Dahlia M
DM
Schwinn
Debra A
DA
Newman
Mark F
MF
D000368:Aged; D000483:Alleles; D002097:C-Reactive Protein / Q000235:genetics; D002315:Cardiopulmonary Bypass; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D015999:Multivariate Analysis; D009154:Mutation; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011183:Postoperative Complications; D012306:Risk; D012737:Sex Factors; D020521:Stroke / Q000235:genetics*; D013903:Thoracic Surgery
D015850:Interleukin-6; D002097:C-Reactive Protein