Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan.
Keio Spine Research Group, Tokyo, Japan.
Spine (Phila Pa 1976). 2019 Dec 1;44(23):1623-1629. doi: 10.1097/BRS.0000000000003179.
Genetic case-control study of single nucleotide polymorphisms (SNPs).
To examine the association of previously reported susceptibility genes for adolescent idiopathic scoliosis (AIS) and intervertebral disc (IVD) degeneration with adult spinal deformity (ASD).
ASD 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.
ASD 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.
Among 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).
rs11190870 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.
单核苷酸多态性（SNP）的遗传病例对照研究。
研究先前报道的青少年特发性脊柱侧凸（AIS）和椎间盘（IVD）退变易感基因与成人脊柱畸形（ASD）的相关性。
ASD 是一种随着年龄增长而发展和进展的脊柱畸形。其病因尚不清楚。最近使用候选基因方法报道了几个 ASD 易感基因；然而，样本量较小，并且与 ASD 发展的相关性尚未确定。
ASD 定义为站立位 X 线片 Cobb 角大于 15°的结构性脊柱侧凸，本研究中患者年龄在 40 至 75 岁之间。排除 20 岁前诊断为脊柱侧凸的患者。我们招募了 356 名日本 ASD 患者和 3341 名健康对照者进行先前报道的 SNPs 的病例对照关联研究。我们通过 Invader 检测技术对四个已知的 AIS 相关 SNP（rs11190870 在 LBX1 中，rs6570507 在 GPR126 中，rs10738445 在 BNC2 中，rs6137473 在 PAX1 中）和三个 IVD 退变相关 SNP（rs1245582 在 CHST3 中，rs2073711 在 CILP 中，rs1676486 在 COL11A1 中）进行了基因分型。
在 AIS 相关 SNP 中，rs11190870 和 rs6137473 与 ASD 呈强关联和名义关联（P = 1.44×10，1.00×10，分别）。在 IVD 退变相关 SNP 中，rs1245582 和 rs2073711 与 ASD 无关联，而 rs1676486 则呈名义关联（P = 1.10×10）。在亚组分析中，rs11190870 与小胸弯 Cobb 角大于 20°（P = 1.44×10）和左侧凸腰椎曲度（P = 6.70×10）显著相关，与 L1 以上的顶椎高度呈名义相关（P = 1.80×10）。
LBX1 中的强 AIS 易感 SNP rs11190870 也可能是 ASD 的易感 SNP。因此，ASD 和 AIS 可能具有共同的遗传背景。
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