Meta-analysis of the plasminogen activator inhibitor-1 (PAI-1) gene with insertion/deletion 4G/5G polymorphism and its susceptibility to ischemic stroke in Thai population

Abstract

Backgrounds: Plasminogen activator inhibitor-1 (PAI-1) gene was reported to associate with ischemic stroke, particularly the insertion/deletion 4G/5G promoter polymorphism. However, because of the complexity and multifactorial nature of stroke, many previous studies showed inconsistent results. Objectives: We investigated whether PAI-1 gene polymorphism is associated with ischemic stroke by genetic association and meta-analysis in Thais. Methods: A case-control genetic association study on PAI-1 polymorphism was conducted. It contains 179 patients with ischemic stroke and 229 healthy controls. We also conducted a meta-analysis by combining the results from our work with other published association studies obtained between 1994 and 2010. Results: The genetic association studies on PAI-1 polymorphism on the Thai samples indicate marginal odds ratio between the PAI-1 polymorphisms and the risk of ischemic stroke. Combining our samples with all previously reported PAI-1 association studies, we did not find any genetic model significant by the lambda method. However, the allele-based method showed the recessive genetic model to be significant for the Asian-derived population when analyzed separately from Caucasians. Conclusions: From the meta-analysis on our Thai data combined with other publications, it can be concluded that the homozygous-4G polymorphism is a risk factor for ischemic stroke in Asian, but not Caucasian populations. However, according to marginal odds ratio results, the cryptic genetic contribution, or other missing heritability should be considered for the study of ischemic stroke for Thais. Keywords: Genetic polymorphism, ischemic stroke, meta-analysis, Plasminogen activator inhibitor type 1 (PAI-1), SERPINE