SNPs in BRAP associated with risk of myocardial infarction in Asian populations.
Myocardial infarction is a common disease and among the leading causes of death in the world. We previously reported association of variants in LGALS2, encoding galectin-2, with myocardial infarction susceptibility in a case-control association study in a Japanese population. Here we identify BRAP (BRCA1-associated protein) as a galectin-2-binding protein. We report an association of SNPs in BRAP with myocardial infarction risk in a large Japanese cohort (P = 3.0 x 10(-18), OR = 1.48, 2,475 cases and 2,778 controls), with replication in additional Japanese and Taiwanese cohorts (P = 4.4 x 10(-6), 862 cases and 1,113 controls and P = 4.7 x 10(-3), 349 cases and 994 controls, respectively). BRAP expression was observed in smooth muscle cells (SMCs) and macrophages in human atherosclerotic lesions. BRAP knockdown by siRNA using cultured coronary endothelial cells suppressed activation of NF-kappaB, a central mediator of inflammation.
Ozaki
Kouichi
K
Laboratory for Cardiovascular Diseases, Center for Genomic Medicine, RIKEN, Yokohama 230-0045, Japan.
Sato
Hiroshi
H
Inoue
Katsumi
K
Tsunoda
Tatsuhiko
T
Sakata
Yasuhiko
Y
Mizuno
Hiroya
H
Lin
Tsung-Hsien
TH
Miyamoto
Yoshinari
Y
Aoki
Asako
A
Onouchi
Yoshihiro
Y
Sheu
Sheng-Hsiung
SH
Ikegawa
Shiro
S
Odashiro
Keita
K
Nobuyoshi
Masakiyo
M
Juo
Suh-Hang H
SH
Hori
Masatsugu
M
Nakamura
Yusuke
Y
Tanaka
Toshihiro
T
D000818:Animals; D001208:Asia; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019556:COS Cells; D016022:Case-Control Studies; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D009203:Myocardial Infarction / Q000235:genetics*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000502:physiology*; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000494:pharmacology; D012307:Risk Factors; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism
D016328:NF-kappa B; D034741:RNA, Small Interfering; C111164:BRAP protein, human; D044767:Ubiquitin-Protein Ligases