| Mutation of ARHGAP9 in patients with coronary spastic angina. | |
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MedLine Citation:
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PMID: 19911011 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-11-13 |
Journal Detail:
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Title: Journal of human genetics Volume: 55 ISSN: 1435-232X ISO Abbreviation: J. Hum. Genet. Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2010-01-25 Completed Date: 2010-04-05 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9808008 Medline TA: J Hum Genet Country: Japan |
Other Details:
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Languages: eng Pagination: 42-9 Citation Subset: IM |
Affiliation:
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Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, 65 Tsurumai, Showa-ku, Nagoya, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acetylcholine
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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:
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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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