• Kazuki Takeda, Ikuyo Kou, Naobumi Hosogane, Nao Otomo, Mitsuru Yagi, Shinjiro Kaneko, Hitoshi Kono, Masayuki Ishikawa, Yohei Takahashi, Takeshi Ikegami, Kenya Nojiri, Eijiro Okada, Haruki Funao, Kunimasa Okuyama, Takashi Tsuji, Nobuyuki Fujita, Narihito Nagoshi, Osahiko Tsuji, Yoji Ogura, Ken Ishii, Masaya Nakamura, Morio Matsumoto, Shiro Ikegawa, and Kota Watanabe.
• Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan.
• Spine. 2019 Dec 1; 44 (23): 1623-1629.

Study DesignGenetic case-control study of single nucleotide polymorphisms (SNPs).ObjectiveTo examine the association of previously reported susceptibility genes for adolescent idiopathic scoliosis (AIS) and intervertebral disc (IVD) degeneration with adult spinal deformity (ASD).Summary Of Background DataASD is a spinal deformity that develops and progresses with age. Its etiology is unclear. Several ASD susceptibility genes were recently reported using a candidate gene approach; however, the sample sizes were small and associations with ASD development were not determined.MethodsASD was defined as structural scoliosis with a Cobb angle more than 15° on standing radiographs, taken of patients at age 40 to 75 years in this study. Subjects in whom scoliosis was diagnosed before age 20 were excluded. We recruited 356 Japanese ASD subjects and 3341 healthy controls for case-control association studies of previously reported SNPs. We genotyped four known AIS-associated SNPs (rs11190870 in LBX1, rs6570507 in GPR126, rs10738445 in BNC2, and rs6137473 in PAX1) and three IVD degeneration-associated SNPs (rs1245582 in CHST3, rs2073711 in CILP, and rs1676486 in COL11A1) by the Invader assay.ResultsAmong the AIS-associated SNPs, rs11190870 and rs6137473 showed strong and nominal associations with ASD (P = 1.44 × 10, 1.00 × 10, respectively). Of the IVD degeneration-associated SNPs, rs1245582 and rs2073711 showed no association with ASD, while rs1676486 showed a nominal association (P = 1.10 × 10). In a subgroup analysis, rs11190870 was significantly associated with a Cobb angle more than 20° in the minor thoracic curve (P = 1.44 × 10) and with a left convex lumbar curve (P = 6.70 × 10), and nominally associated with an apical vertebra higher than L1 (P = 1.80 × 10).Conclusionrs11190870 in LBX1, a strong susceptibility SNP for AIS, may also be a susceptibility SNP for ASD. Thus, ASD and AIS may share a common genetic background.Level Of Evidence4.

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