A functional variant in MIR4300HG, the host gene of microRNA MIR4300 is associated with progression of adolescent idiopathic scoliosis

作者：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^*

来源：Human Molecular Genetics, 2017, 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 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.

• 出版日期2017-10-15