Effect of single nucleotide polymorphisms of the prostacyclin receptor gene on platelet activation in Japanese healthy subjects and patients with cerebral infarction.

Abstract

Cerebral infarction (CI) is a complex multifactorial disorder that is thought to result from the interaction of various environmental factors and an individual's genetic make-up, including genes associated with platelet activation. In order to clarify whether single nucleotide polymorphisms (SNPs) of the prostacyclin receptor (IP) gene affects platelet activation in ischemic stroke, we investigated the relationship between platelet function and genetic polymorphism of the coding sequence of the IP gene in 64 Japanese patients with CI and 54 healthy subjects. We determined the entire nucleotide sequence of the IP gene in healthy Japanese subjects, and found that an adenine (A) to cytosine (C) substitution at base 984 (A984C) in exon 3 is the most frequent SNP. Using flow cytometry, the power-transformed mean percentage of PAC-1-positive platelets, [PAC-1](1/3), was significantly higher in healthy subjects with the C/C genotype than in healthy subjects with the A/A genotype (p ≤ 0.05), although there was no significant difference in patients with CI between these two genotypes. Furthermore, we genotyped 158 control patients and 106 patients with CI. The homozygous C/C genotype was more frequently found in the CI group (46.2%) than in the healthy control group (17.1%; p < 0.001). The present report is the first to show an association between the A984C polymorphism of the IP gene and platelet activation in Japanese subjects. This polymorphism may be clinically significant in disorders in which prostacyclin plays a key role, such as CI.

• Authors: Mie Shimizu, Shinichi Yoshimura, Shunya Takizawa, Saori Kohara, Hidetoshi Inoko, Shigeharu Takagi
• Journal: Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia (J Clin Neurosci) Vol. 20 Issue 6 Pg. 851-6 (Jun 2013) ISSN: 1532-2653 [Electronic] Scotland
• PMID: 23628440 (Publication Type: Journal Article)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• (4-benzylpiperazin-1-yl)acetic acid (3-allyl-2-hydroxybenzylidene)hydrazine
• Hydrazones
• P-Selectin
• PTGIR protein, human
• Piperazines
• Receptors, Epoprostenol
• Receptors, Prostaglandin
• SELP protein, human

Topics

• Adult
• Cerebral Infarction (genetics)
• Female
• Flow Cytometry
• Gene Frequency
• Genetic Predisposition to Disease
• Genotype
• Humans
• Hydrazones (metabolism)
• Japan
• Male
• Middle Aged
• P-Selectin (metabolism)
• Piperazines (metabolism)
• Platelet Activation (genetics)
• Polymorphism, Single Nucleotide (genetics)
• Receptors, Epoprostenol
• Receptors, Prostaglandin (genetics)