title: A functional SNP in ITIH3 is associated with susceptibility to myocardial infarction.
abstract: Myocardial infarction (MI) results from complex interactions of multiple genetic and environmental factors. To disclose genetic backgrounds of MI, we performed a large-scale, case-control association study using 52,608 gene-based single-nucleotide polymorphism (SNP) markers, and identified a candidate SNP located on chromosome 3p21.2-p21.1. Subsequent linkage-disequilibrium mapping indicated very significant association between MI and a SNP in exon 2 of the inter-alpha (globulin) inhibitor 3 gene (ITIH3; chi(2) = 24.88, P = 6.1 x 10(-7), 3,353 affected individuals versus 3,807 controls). In vitro functional analyses showed that this SNP enhanced the transcriptional level of the ITIH3 gene. Furthermore, we found expression of the ITIH3 protein in the vascular smooth muscle cells and macrophages in the human atherosclerotic lesions, suggesting ITIH3 SNP to be a novel genetic risk factor of MI.
authors.affiliation: Laboratory for Cardiovascular Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.|Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ebana
authors.affiliation: Laboratory for Cardiovascular Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
authors.forename: Kouichi
authors.initials: K
authors.lastname: Ozaki
authors.affiliation: Department of Cardiology, Kokura Memorial Hospital, Kitakyushu, 802-8555, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Inoue
authors.affiliation: Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sato
authors.affiliation: Laboratory for Pharmacogenetics, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo, Japan.
authors.forename: Aritoshi
authors.initials: A
authors.lastname: Iida
authors.affiliation: Laboratory for Cardiovascular Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
authors.forename: Htay
authors.initials: H
authors.lastname: Lwin
authors.affiliation: Laboratory for Pharmacogenetics, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Saito
authors.affiliation: Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Hiroya
authors.initials: H
authors.lastname: Mizuno
authors.affiliation: Laboratory for Statistical Analysis, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takahashi
authors.affiliation: Laboratory for Statistical Analysis, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Laboratory for Bone and Joint Disease, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo, Japan.
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Miyamoto
authors.affiliation: Laboratory for Bone and Joint Disease, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegawa
authors.affiliation: Department of Cardiology, Kokura Memorial Hospital, Kitakyushu, 802-8555, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Odashiro
authors.affiliation: Department of Cardiology, Kokura Memorial Hospital, Kitakyushu, 802-8555, Japan.
authors.forename: Masakiyo
authors.initials: M
authors.lastname: Nobuyoshi
authors.affiliation: Laboratory for Statistical Analysis, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kamatani
authors.affiliation: Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Hori
authors.affiliation: Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Isobe
authors.affiliation: Laboratory for Pharmacogenetics, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Tokyo, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Laboratory for Cardiovascular Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan. toshitan@ims.u-tokyo.ac.jp.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Tanaka
mesh_terms: D000510:Alpha-Globulins / Q000235:genetics* / Q000378:metabolism; D050197:Atherosclerosis / Q000473:pathology; D016022:Case-Control Studies; D005091:Exons / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006239:Haplotypes; D006801:Humans; D007438:Introns / Q000235:genetics; D009203:Myocardial Infarction / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D000510:Alpha-Globulins; C011877:inter-alpha-inhibitor