Genetic polymorphisms and the risk of stroke after cardiac surgery.

Published

Journal Article

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.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.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).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.

Full Text

Duke Authors

Cited Authors

  • Grocott, HP; White, WD; Morris, RW; Podgoreanu, MV; Mathew, JP; Nielsen, DM; Schwinn, DA; Newman, MF; Perioperative Genetics and Safety Outcomes Study (PEGASUS) Investigative Team,

Published Date

  • September 2005

Published In

Volume / Issue

  • 36 / 9

Start / End Page

  • 1854 - 1858

PubMed ID

  • 16051899

Pubmed Central ID

  • 16051899

Electronic International Standard Serial Number (EISSN)

  • 1524-4628

International Standard Serial Number (ISSN)

  • 0039-2499

Digital Object Identifier (DOI)

  • 10.1161/01.str.0000177482.23478.dc

Language

  • eng