Document Detail


Mutation of ARHGAP9 in patients with coronary spastic angina.
MedLine Citation:
PMID:  19911011     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Coronary artery spasm has an important function in the etiology of variant angina and other acute coronary syndromes. Abnormal activation of Rho-family GTPases has been observed in cardiovascular disorders, but the function of genetic variability in Rho-family GTPases remains to be evaluated in cardiovascular disorders. We examined the genetic variability of Rho-family GTPases and their regulators in coronary artery spasm. We performed a comprehensive candidate gene analysis of 67 single nucleotide polymorphisms with amino-acid substitution in Rho-family GTPases and their regulators in 103 unrelated Japanese patients with acetylcholine-induced coronary artery spasm and 102 control Japanese subjects without acetylcholine-induced coronary artery spasm. We noted an association of the single nucleotide polymorphism of ARHGAP9 (rs11544238, Ala370Ser) with coronary artery spasm (odds ratio =2.67). We found that ARHGAP9 inactivated Rac as RacGAP and that the mRNA level of ARHGAP9 was strongly detected in hematopoietic cells. ARHGAP9 negatively regulated cell migration. The Ala370Ser polymorphism counteracted ARHGAP9-reduced cell migration, spreading and adhesion. The Ala370Ser polymorphism in the ARHGAP9 gene is associated with coronary artery spasm. These data suggest that the polymorphism of ARHGAP9 has a critical function in the infiltration of hematopoietic cells into the endothelium and inflammation leading to endothelial dysfunction.
Authors:
Mikito Takefuji; Hiroyuki Asano; Kazutaka Mori; Mutsuki Amano; Katsuhiro Kato; Takashi Watanabe; Yasuhiro Morita; Akira Katsumi; Toshiki Itoh; Tadaomi Takenawa; Akihiro Hirashiki; Hideo Izawa; Kozo Nagata; Haruo Hirayama; Fumimaro Takatsu; Tomoki Naoe; Mitsuhiro Yokota; Kozo Kaibuchi
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-11-13
Journal Detail:
Title:  Journal of human genetics     Volume:  55     ISSN:  1435-232X     ISO Abbreviation:  J. Hum. Genet.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2010-01-25     Completed Date:  2010-04-05     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9808008     Medline TA:  J Hum Genet     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  42-9     Citation Subset:  IM    
Affiliation:
Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, 65 Tsurumai, Showa-ku, Nagoya, Japan.
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MeSH Terms
Descriptor/Qualifier:
Acetylcholine / administration & dosage
Angina Pectoris, Variant / genetics,  physiopathology
Coronary Angiography
Coronary Vasospasm / chemically induced,  genetics*,  physiopathology
Female
GTPase-Activating Proteins / genetics*,  metabolism
Genetic Predisposition to Disease*
Hela Cells
Humans
Japan
Jurkat Cells
Male
Mutation*
Polymorphism, Single Nucleotide
Chemical
Reg. No./Substance:
0/ARHGAP9 protein, human; 0/GTPase-Activating Proteins; 51-84-3/Acetylcholine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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