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 × 10−4, 1.00 × 10−2, respectively). Of the IVD degeneration-associated SNPs, rs1245582 and rs2073711 showed no association with ASD, while rs1676486 showed a nominal association (P = 1.10 × 10−2). In a subgroup analysis, rs11190870 was significantly associated with a Cobb angle more than 20° in the minor thoracic curve (P = 1.44 × 10−4) and with a left convex lumbar curve (P = 6.70 × 10−4), and nominally associated with an apical vertebra higher than L1 (P = 1.80 × 10−2).
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.
Level of Evidence: 4
We investigated the genetic association between adult spinal deformity (ASD) and adolescent idiopathic scoliosis (AIS) or intervertebral disc (IVD) degeneration. A known AIS-associated single nucleotide polymorphism in LBX1 was clearly associated with ASD. Therefore, LBX1 may be a susceptibility gene for ASD.
∗Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan
†Keio Spine Research Group, Tokyo, Japan
‡Laboratory of Bone and Joint Diseases, Center for Integrative Medical Sciences, RIKEN, Tokyo, Japan
§Department of Orthopaedic Surgery, National Defense Medical College, Saitama, Japan
¶Department of Orthopaedic Surgery, National Hospital Organization Murayama Medical Center, Tokyo, Japan
||Department of Orthopaedic Surgery, Medical Corporation Keiyukai Keiyu Orthopaedic Hospital, Gunma, Japan
∗∗Spine and Spinal Cord Center, Mita Hospital, International University of Health and Welfare, Tokyo, Japan
††Spine Center, Japanese Red Cross Shizuoka Hospital, Shizuoka, Japan
‡‡Department of Orthopaedic Surgery, Fussa Hospital, Tokyo, Japan
§§Department of Orthopaedic Surgery, Isehara Kyodo Hospital, Kanagawa, Japan
¶¶Department of Orthopaedic Surgery, Saiseikai Central Hospital, Tokyo, Japan
||||Department of Orthopaedic Surgery, Kawasaki Municipal Hospital, Kanagawa, Japan
∗∗∗Department of Orthopaedic Surgery, Sizuoka City Shimizu Hospital, Shizuoka, Japan
†††Department of Orthopaedic Surgery, Fujita Health University Hospital, Aichi, Japan
‡‡‡Department of Orthopaedic Surgery, International University of Health and Welfare, Tokyo, Japan.
Address correspondence and reprint requests to Shiro Ikegawa, MD, PhD, Laboratory of Bone and Joint Diseases, Center for Integrative Medical Sciences, RIKEN, 4-6-1 Sirokanedai, Minato-ku, Tokyo 108-8639, Japan; E-mail: email@example.com; Kota Watanabe, MD, PhD, Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan; E-mail: firstname.lastname@example.org
Received 18 December, 2018
Revised 20 May, 2019
Accepted 3 June, 2019
The manuscript submitted does not contain information about medical device(s)/drug(s).
The Japan Orthopaedics and Traumatology Foundation and Grant-in-Aid for Scientific Research ((C) 16K08251) from the Japan Society for the Promotion of Science funds were received in support of this work.
No relevant financial activities outside the submitted work.