Abstract
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 population1. 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 × 10−18, OR = 1.48, 2,475 cases and 2,778 controls), with replication in additional Japanese and Taiwanese cohorts (P = 4.4 × 10−6, 862 cases and 1,113 controls and P = 4.7 × 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-κB, a central mediator of inflammation.
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Acknowledgements
We thank M. Takahashi, M. Yoshii, S. Abiko, W. Yamanobe, R. Ohishi, M. Watabe and T. Furusho for their assistance. We also thank all the other members of Center for Genomic Medicine, RIKEN and OACIS for their contribution to the completion of our study. We are also grateful to members of The Rotary Club of Osaka-Midosuji District 2660 Rotary International in Japan for supporting our study. This work was supported in part by grants from the Takeda Science Foundation, the Uehara Science Foundation, the Japanese Millennium Project and the Ministry of Education, Science, Sports, Culture and Technology of Japan and NHRI-Ex96-9607PI (Taiwan).
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K. Ozaki performed most of the experiments and wrote the manuscript; H.S., Y.S., H.M., T.-H.L., Y.M., S.-H.S., S.I., S.-H.H.J. and M.H. managed DNA samples and clinical information; K.I., K. Odashiro and M.N. performed the immunohistochemistry; T. Tsunoda performed the statistical analyses; A.A. and Y.O. performed the data analyses; Y.N. contributed to SNP discovery and preparation of the manuscript; and T. Tanaka supervised this study.
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Ozaki, K., Sato, H., Inoue, K. et al. SNPs in BRAP associated with risk of myocardial infarction in Asian populations. Nat Genet 41, 329–333 (2009). https://doi.org/10.1038/ng.326
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DOI: https://doi.org/10.1038/ng.326
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