微小RNA MIR4300的宿主基因MIR4300HG中的一个功能性变体与青少年特发性脊柱侧凸的进展相关。
A functional variant in MIR4300HG, the host gene of microRNA MIR4300 is associated with progression of adolescent idiopathic scoliosis.
作者信息
Ogura Yoji, Kou Ikuyo, Takahashi Yohei, Takeda Kazuki, Minami Shohei, Kawakami Noriaki, Uno Koki, Ito Manabu, Yonezawa Ikuho, Kaito Takashi, Yanagida Haruhisa, Watanabe Kei, Taneichi Hiroshi, Harimaya Katsumi, Taniguchi Yuki, Kotani Toshiaki, Tsuji Taichi, Suzuki Teppei, Sudo Hideki, Fujita Nobuyuki, Yagi Mitsuru, Chiba Kazuhiro, Kubo Michiaki, Kamatani Yoichiro, Nakamura Masaya, Matsumoto Morio, Watanabe Kota, Ikegawa Shiro
机构信息
Laboratory of Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo 108-8639, Japan.
Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan.
出版信息
Hum Mol Genet. 2017 Oct 15;26(20):4086-4092. doi: 10.1093/hmg/ddx291.
Adolescent idiopathic scoliosis (AIS) is a common spinal deformity affecting millions of children. Since treatment and prognosis of AIS depend on curve progression, identifying factors related to AIS curve progression is important in its management. Although several genetic loci for AIS occurrence are reported, no locus for curve progression has been identified. To identify genes associated with AIS progression, we conducted a genome-wide association study followed by a replication study using a total of 2,543 AIS subjects who were evaluated for the curve progression. We identified a significantly associated locus on chromosome 11q14.1 (P = 1.98 × 10-9, odds ratio = 1.56). In silico and in vitro analyses identified a functional variant, rs35333564 in MIR4300HG, the host gene of a microRNA, MIR4300. The genomic region containing rs35333564 had enhancer activity, which was decreased in its risk allele. Our data suggest that decrease of MIR4300 is related to AIS progression.
青少年特发性脊柱侧凸（AIS）是一种常见的脊柱畸形，影响着数百万儿童。由于AIS的治疗和预后取决于曲线进展，因此识别与AIS曲线进展相关的因素对其管理至关重要。尽管已报道了几个与AIS发生相关的基因位点，但尚未发现与曲线进展相关的位点。为了识别与AIS进展相关的基因，我们进行了一项全基因组关联研究，随后进行了一项复制研究，共纳入了2543名接受曲线进展评估的AIS受试者。我们在11号染色体q14.1上鉴定出一个显著相关的位点（P = 1.98×10-9，优势比 = 1.56）。通过计算机模拟和体外分析，我们在MIR4300HG（一种 microRNA，即MIR4300的宿主基因）中鉴定出一个功能性变异rs35333564。包含rs35333564的基因组区域具有增强子活性，其风险等位基因的活性降低。我们的数据表明，MIR4300的减少与AIS进展有关。
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