Interactions among Variants in Eicosanoid Genes Increase Risk of Atherothrombotic Stroke in Chinese Populations.

<bold>Background: </bold>Eicosanoids are lipid mediators that may play a role in ischemic stroke (IS). However, the association of variants in eicosanoid genes and these interactions with IS risk has not been investigated. The aim of the present study was to investigate the association of 11 variants in eicosanoid genes with IS and to determine whether these gene-gene interactions increase the risk of IS.<bold>Methods: </bold>Eleven variants in prostaglandin H synthase-1 (PTGS1), PTGS2, thromboxane A2 synthase (TBXAS1), prostacyclin synthase (PTGIS), and prostaglandin E synthase (PTGES) genes were examined using mass spectrometry method in 297 patients with atherothrombotic stroke and 291 controls. Gene-gene interactions were analyzed using generalized multifactor dimensionality reduction (GMDR) method. Platelet aggregation and platelet-leukocyte aggregates were measured on admission.<bold>Results: </bold>There were no significant differences in the genotype distributions of the 11 variants between patients and controls. However, GMDR analysis showed a significant gene-gene interaction among rs20417, rs5602, and rs41708, which scored 10 for cross-validation consistency and 9 for the sign test (P = .014). Logistic regression analysis showed that high-risk interaction among rs20417, rs5602, and rs41708 was an independent risk factor for atherothrombotic stroke (OR = 2.45, 95% CI: 1.33-3.27, P = .019). The high-risk interactive genotypes were associated with higher platelet aggregation and platelet-leukocyte aggregates.<bold>Conclusions: </bold>PTGS2 rs20417, PTGIS rs5602, and TBXAS1 rs41708 three-locus interactions may confer a higher risk for atherothrombotic stroke. The combinatorial analysis used in this study may be helpful to elucidate complex genetic risk for IS. [ABSTRACT FROM AUTHOR]