Haplotypes of the plasminogen activator gene associated with ischemic stroke

Kosuke Saito; Tomohiro Nakayama; Naoyuki Sato; Akihiko Morita; Teruyuki Takahashi; Masayoshi Soma; Ron Usami

doi:10.1160/TH05-12-0830

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2006; 96(03): 331-336
DOI: 10.1160/TH05-12-0830

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Haplotypes of the plasminogen activator gene associated with ischemic stroke

Kosuke Saito

¹Division of Molecular Diagnostics, Advanced Medical Research Center, Nihon University School of Medicine, Tokyo, Japan

²Department of Biological Applied Chemistry, Toyo University Graduate School of Engineering, Saitama, Japan

,

Tomohiro Nakayama

¹Division of Molecular Diagnostics, Advanced Medical Research Center, Nihon University School of Medicine, Tokyo, Japan

,

Naoyuki Sato

¹Division of Molecular Diagnostics, Advanced Medical Research Center, Nihon University School of Medicine, Tokyo, Japan

,

Akihiko Morita

³Department of Neurology, Division of Neurology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan

,

Teruyuki Takahashi

⁴Department of Neurology, Graduate School of Medicine, Nihon University, Tokyo, Japan

,

Masayoshi Soma

⁵Division of Nephrology and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan

,

Ron Usami

²Department of Biological Applied Chemistry, Toyo University Graduate School of Engineering, Saitama, Japan

› Author Affiliations

Abstract

Summary

Ischemic stroke (IS) is thought to be a multifactorial disorder associated with genetic backgrounds and environmental factors. In the circulating plasma, tissue plasminogen activator (tPA) catalyzes the reaction from plasminogen to plasmin. If there is a functional disability of tPA, induction of thrombosis and infarction disorders can occur. The aim of this study was to performa haplotype-based case-control study using single nucleotide polymorphisms (SNPs) in the human tPA gene, and to assess the association between the tPA gene and IS. We genotyped 182 IS individuals and 403 controls for five SNPs in the human tPA gene, rs7007329, rs732612, rs8178750, rs2020922, and rs4471024. Using these five SNPs, a haplotype-based case control study was performed. There were seven SNP combinations that exhibited significant differences in the overall distribution between the IS and control groups. Linkage disequilibrium analysis showed that the combination of rs7007329 and rs8178750 was useful in identification of the susceptibility haplotype. The frequency of the G-T haplotype at rs7007329-rs8178750 was significantly higher in the IS group (1.2%) as compared to the control group (0.0%) (p=0.003).Diplotype analysis also showeda significant association of the diplotype with the G-T haplotype at rs7007329-rs8178750 (OR:11.4, 95%CI:1.32–97.9, p=0.013). These results suggest that the G-T haplotype at rs7007329-rs8178750 of the tPA gene isa genetic marker for IS, and that tPA ora neighboring gene isa susceptibility gene for IS.

Keywords

Tissue plasminogen activator - ischemic stroke - haplotypes - association studies - genetics

Full Text

References

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