Polymorphisms in platelet glycoprotein 1balpha and factor VII and risk of ischemic stroke: a meta-analysis.
OBJECTIVE
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.
Maguire
Jane M
JM
Neurosciences Department, Gosford Hospital, Northern Sydney Central Coast Health Service, Gosford NSW 2250, Australia. jmaguire@nsccahs.health.nsw.gov.au
Thakkinstian
Ammarin
A
Sturm
Jon
J
Levi
Christopher
C
Lincz
Lisa
L
Parsons
Mark
M
Whyte
Scott
S
Attia
John
J
D002545:Brain Ischemia / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D004252:DNA Mutational Analysis; D005167:Factor VII / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000235:genetics*; D019038:Platelet Glycoprotein GPIb-IX Complex; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D020521:Stroke / Q000097:blood / Q000235:genetics* / Q000503:physiopathology
D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D019038:Platelet Glycoprotein GPIb-IX Complex; C094990:adhesion receptor; D005167:Factor VII