The PAI-1 4G/5G gene polymorphism and ischemic stroke: an association study and meta-analysis.
To investigate whether the 4G/5G polymorphism of plasminogen activator inhibitor type 1 (PAI-1) and the -7351 C/T polymorphism of tissue-type plasminogen activator (t-PA) are associated with ischemic stroke, we conducted a case-control study of 190 hospital cases of first-ever ischemic stroke and 185 community-based controls. Our findings do not indicate any association between the PAI-1 or t-PA polymorphisms and risk of stroke. Adding our PAI-1 results to previous studies in a meta-analysis indicated a strong association between this polymorphism and ischemic stroke (P = .0002), with no publication bias but with extreme heterogeneity. There was evidence of stroke association with the PAI-1 4G/5G locus. Strong heterogeneity indicates the need to address other issues, including association with particular stroke subtypes or linkage disequilibrium (LD) with another causative allele. The results also sound a cautionary note that varying LD structure across populations may obscure the relationship with a causative locus, and that future meta-analyses need to look beyond a simple pooled estimate.
Attia
John
J
Centre for Clinical Epidemiology & Biostatistics, School of Medicine and Public Health, University of Newcastle, Newcastle NSW Australia. John.Attia@newcastle.edu.au <John.Attia@newcastle.edu.au>
Thakkinstian
Ammarin
A
Wang
Yang
Y
Lincz
Lisa
L
Parsons
Mark
M
Sturm
Jonathan
J
McGettigan
Patricia
P
Scott
Rodney
R
Meldrum
Cliff
C
Levi
Christopher
C
D000328:Adult; D000368:Aged; D000483:Alleles; D002545:Brain Ischemia / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D009517:New South Wales / Q000453:epidemiology; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics* / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D017384:Sequence Deletion; D010959:Tissue Plasminogen Activator / Q000235:genetics* / Q000502:physiology
D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D010959:Tissue Plasminogen Activator