BACKGROUND AND PURPOSE: Platelets and components of the coagulation cascade are known to be instrumental in the pathogenesis of arterial occlusive disorders. The aim of this meta-analysis is to test the hypothesis that genetic variation in the platelet glycoprotein 1balpha and Factor VII genes influence the occurrence of ischemic stroke. All genetic association studies that examined the R353Q (rs6046) polymorphism of the Factor VII gene and 2 polymorphisms of the platelet glycoprotein (1balpha) gene (Thr/Met rs6065 and Kozak sequence -5 C/T rs2243093) in relation to ischemic stroke were examined. METHODS: Electronic databases Embase, Medline, and HuGEnet were searched for all years up until June 2006 for all studies that evaluated any of these candidate genes and stroke. RESULTS: Pooled ORs were calculated with 95% CIs using both fixed and random effects models. Meta-analysis for Factor VII (R353Q) did not detect any effect on ischemic stroke risk. Further estimation resulted in pooled OR(1) QQ versus RR=0.9 (95% CI: 0.4 to 1.9) and pooled OR(2) for RQ versus RR=0.9 (95% CI: 0.6 to 1.4). These results were robust and homogeneous. Pooling ORs for the platelet glycoprotein 1balpha Kozak variant -5 T/C polymorphism showed extreme heterogeneity with differing effect directions across studies. Fisher's method of pooling was therefore used to calculate a combined probability value, which was highly significant (P<0.001). The pooled OR for platelet glycoprotein 1balpha Met/Met v Thr/Thr was 1.0 to 2.0, depending on the sensitivity analyses, and for Thr/Met versus Thr/Thr, the pooled OR was between 1.3 and 1.4. These results were consistent, reasonably robust, and implied a dominant genetic effect. CONCLUSIONS: This analysis provides strong evidence that the Factor VII R353Q gene polymorphism is not associated with ischemic stroke, that the Thr/Met polymorphism of GP1balpha is associated with ischemic stroke in a dominant genetic model, and that the Kozak sequence polymorphism of GP1balpha may be close to another causative locus that is associated with ischemic stroke.
BACKGROUND AND PURPOSE: Platelets and components of the coagulation cascade are known to be instrumental in the pathogenesis of arterial occlusive disorders. The aim of this meta-analysis is to test the hypothesis that genetic variation in the platelet glycoprotein 1balpha and Factor VII genes influence the occurrence of ischemic stroke. All genetic association studies that examined the R353Q (rs6046) polymorphism of the Factor VII gene and 2 polymorphisms of the platelet glycoprotein (1balpha) gene (Thr/Met rs6065 and Kozak sequence -5 C/T rs2243093) in relation to ischemic stroke were examined. METHODS: Electronic databases Embase, Medline, and HuGEnet were searched for all years up until June 2006 for all studies that evaluated any of these candidate genes and stroke. RESULTS: Pooled ORs were calculated with 95% CIs using both fixed and random effects models. Meta-analysis for Factor VII (R353Q) did not detect any effect on ischemic stroke risk. Further estimation resulted in pooled OR(1) QQ versus RR=0.9 (95% CI: 0.4 to 1.9) and pooled OR(2) for RQ versus RR=0.9 (95% CI: 0.6 to 1.4). These results were robust and homogeneous. Pooling ORs for the platelet glycoprotein 1balpha Kozak variant -5 T/C polymorphism showed extreme heterogeneity with differing effect directions across studies. Fisher's method of pooling was therefore used to calculate a combined probability value, which was highly significant (P<0.001). The pooled OR for platelet glycoprotein 1balpha Met/Met v Thr/Thr was 1.0 to 2.0, depending on the sensitivity analyses, and for Thr/Met versus Thr/Thr, the pooled OR was between 1.3 and 1.4. These results were consistent, reasonably robust, and implied a dominant genetic effect. CONCLUSIONS: This analysis provides strong evidence that the Factor VII R353Q gene polymorphism is not associated with ischemic stroke, that the Thr/Met polymorphism of GP1balpha is associated with ischemic stroke in a dominant genetic model, and that the Kozak sequence polymorphism of GP1balpha may be close to another causative locus that is associated with ischemic stroke.
Authors: Kira C Taylor; Leslie A Lange; Delilah Zabaneh; Ethan Lange; Brendan J Keating; Weihong Tang; Nicholas L Smith; Joseph A Delaney; Meena Kumari; Aroon Hingorani; Kari E North; Mika Kivimaki; Russell P Tracy; Christopher J O'Donnell; Aaron R Folsom; David Green; Steve E Humphries; Alexander P Reiner Journal: Hum Mol Genet Date: 2011-06-15 Impact factor: 6.150
Authors: N A Zakai; L Lange; W T Longstreth; E S O'Meara; J L Kelley; M Fornage; D Nikerson; M Cushman; A P Reiner Journal: J Thromb Haemost Date: 2011-02 Impact factor: 5.824
Authors: Marlene S Williams; Ethan J Weiss; Marc S Sabatine; Daniel I Simon; Wadie F Bahou; Lewis C Becker; Leslie V Parise; Harold L Dauerman; Patricia A French; Susan S Smyth; Richard C Becker Journal: Arterioscler Thromb Vasc Biol Date: 2010-12 Impact factor: 8.311
Authors: Andrea Kopp Lugli; Martin M Brown; Jan Steffel; Linda Büchi; Dorothee Förnzler; Annabelle Dupont; Pascale Gaussem; Marc Forestier; Juerg H Beer Journal: J Thromb Thrombolysis Date: 2011-08 Impact factor: 2.300
Authors: N C Olson; L M Raffield; L A Lange; E M Lange; W T Longstreth; G Chauhan; S Debette; S Seshadri; A P Reiner; R P Tracy Journal: J Thromb Haemost Date: 2017-12-08 Impact factor: 5.824
Authors: Juan Criado-García; Francisco Fuentes; Cristina Cruz-Teno; Antonio García-Rios; Anabel Jiménez-Morales; Javier Delgado-Lista; Pedro Mata; Rodrigo Alonso; José López-Miranda; Francisco Pérez-Jiménez Journal: Lipids Health Dis Date: 2011-04-09 Impact factor: 3.876
Authors: Mar Matarin; W Mark Brown; Hernandez Dena; Angela Britton; Fabienne Wavrant De Vrieze; Thomas G Brott; Robert D Brown; Bradford B Worrall; L Douglas Case; Stephen J Chanock; E Jeffrey Metter; Luigi Ferruci; Dale Gamble; John A Hardy; Stephen S Rich; Andrew Singleton; James F Meschia Journal: Stroke Date: 2009-09-03 Impact factor: 7.914