SNPs in BRAP associated with risk of myocardial infarction in Asian populations
SNPs in BRAP associated with risk of myocardial infarction in Asian populations
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DOI：
10.1038/ng.326
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发表时间：
2009-03-01
期刊：
影响因子：
30.8
通讯作者：
Tanaka, Toshihiro
中科院分区：
文献类型：
--
作者：
Ozaki, Kouichi;Sato, Hiroshi;Tanaka, Toshihiro
心肌梗塞是一种常见疾病，也是世界上导致死亡的主要原因之一。我们之前在日本人群的病例对照关联研究中报道了编码半乳糖凝集素 2 的 LGALS2 变异与心肌梗死易感性的关联 (1)。在这里，我们将 BRAP（BRCA1 相关蛋白）鉴定为半乳糖凝集素 2 结合蛋白。我们在大型日本队列中报告了 BRAP 中的 SNP 与心肌梗死风险之间的关联（P = 3.0 x 10(-18)，OR = 1.48，2,475 例病例和 2,778 名对照），并在其他日本和台湾队列中复制（P = 4.4 x 10(-6)，862 例病例和 1,113 名对照，P = 4.7 x分别为 10(-3)、349 例和 994 例对照）。在人类动脉粥样硬化病变的平滑肌细胞 (SMC) 和巨噬细胞中观察到 BRAP 表达。使用培养的冠状动脉内皮细胞通过 siRNA 敲除 BRAP，抑制了炎症的核心介质 NF-κ B 的激活。
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(1). 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-kappa B, a central mediator of inflammation.