A functional variant in MIR4300HG, the host gene of microRNA MIR4300 is associated with progression of adolescent idiopathic scoliosis
A functional variant in MIR4300HG, the host gene of microRNA MIR4300 is associated with progression of adolescent idiopathic scoliosis
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DOI：
10.1093/hmg/ddx291
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发表时间：
2017-10-15
影响因子：
3.5
通讯作者：
Ikegawa, Shiro
中科院分区：
文献类型：
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作者：
Ogura, Yoji;Kou, Ikuyo;Ikegawa, Shiro
青少年特发性脊柱侧凸（AIS）是一种常见的脊柱畸形，影响数百万儿童。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在其管理中非常重要。虽然有几个AIS发生的遗传位点的报道，没有发现曲线进展的位点。为了识别与AIS进展相关的基因，我们进行了全基因组关联研究，然后对总共2，543名AIS受试者进行了复制研究，这些受试者接受了曲线进展评估。我们在染色体11q14.1上发现了一个显著相关的位点（P = 1.98 × 10（-9），比值比= 1.56）。计算机模拟和体外分析鉴定了MIR 4300 HG中的功能变体rs35333564，MIR 4300 HG是microRNA MIR 4300的宿主基因。含有rs35333564的基因组区域具有增强子活性，其在其风险等位基因中降低。我们的数据表明MIR 4300的降低与AIS进展有关。
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 x 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.