A common variant rs2054564 in ADAMST17 is associated with susceptibility to lumbar spondylosis.

Autor: Taniguchi Y; Department of Orthopedics, The University of Tokyo Hospital, Hongo 7-3-1, Bunkyo-Ku, Tokyo, 113-8655, Japan. taniguchi-tky@umin.ac.jp.; Surgical Center, The University of Tokyo Hospital, Tokyo, 113-8655, Japan. taniguchi-tky@umin.ac.jp., Akune T; Hospital, National Rehabilitation Center for Persons with Disabilities, Tokorozawa, Saitama, 359-0042, Japan., Nishida N; Genome Medical Science Project, National Center for Global Health and Medicine, Tokyo, 162-8655, Japan., Omori G; Department of Health and Sports, Faculty of Health and Science, Niigata University of Health and Welfare, Niigata, 950-3198, Japan., Ha K; Division of Rheumatology, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, 18450, Korea., Ueno K; Genome Medical Science Project, National Center for Global Health and Medicine, Tokyo, 162-8655, Japan., Saito T; Department of Orthopedics, The University of Tokyo Hospital, Hongo 7-3-1, Bunkyo-Ku, Tokyo, 113-8655, Japan., Oichi T; Department of Orthopedics, The University of Tokyo Hospital, Hongo 7-3-1, Bunkyo-Ku, Tokyo, 113-8655, Japan., Koike A; Healthcare Business Division, Hitachi, Ltd., Tokyo, 105-6412, Japan., Mabuchi A; Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-8654, Japan., Oka H; Department of Medical Research and Management for Musculoskeletal Pain, 22nd Century Medical & Research Center, Faculty of Medicine, The University of Tokyo, Tokyo, 113-8654, Japan., Muraki S; Department of Preventive Medicine for Locomotive Organ Disorders, 22nd Century Medical and Research Center, The University of Tokyo, Tokyo, 113-8654, Japan., Oshima Y; Department of Orthopedics, The University of Tokyo Hospital, Hongo 7-3-1, Bunkyo-Ku, Tokyo, 113-8655, Japan., Kawaguchi H; Orthopaedics and Spine Department, Tokyo Neurological Center, Tokyo, 105-0001, Japan., Nakamura K; Department of Orthopedics, Towa Hospital, Tokyo, 120-0003, Japan., Tokunaga K; Genome Medical Science Project, National Center for Global Health and Medicine, Tokyo, 162-8655, Japan., Tanaka S; Department of Orthopedics, The University of Tokyo Hospital, Hongo 7-3-1, Bunkyo-Ku, Tokyo, 113-8655, Japan., Yoshimura N; Department of Preventive Medicine for Locomotive Organ Disorders, 22nd Century Medical and Research Center, The University of Tokyo, Tokyo, 113-8654, Japan.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 Mar 25; Vol. 13 (1), pp. 4900. Date of Electronic Publication: 2023 Mar 25.
DOI: 10.1038/s41598-023-32155-w
Abstrakt: The molecular pathophysiology underlying lumbar spondylosis development remains unclear. To identify genetic factors associated with lumbar spondylosis, we conducted a genome-wide association study using 83 severe lumbar spondylosis cases and 182 healthy controls and identified 65 candidate disease-associated single nucleotide polymorphisms (SNPs). Replication analysis in 510 case and 911 control subjects from five independent Japanese cohorts identified rs2054564, located in intron 7 of ADAMTS17, as a disease-associated SNP with a genome-wide significance threshold (P = 1.17 × 10 -11 , odds ratio = 1.92). This association was significant even after adjustment of age, sex, and body mass index (P = 7.52 × 10 -11 ). A replication study in a Korean cohort, including 123 case and 319 control subjects, also verified the significant association of this SNP with severe lumbar spondylosis. Immunohistochemistry revealed that fibrillin-1 (FBN1) and ADAMTS17 were co-expressed in the annulus fibrosus of intervertebral discs (IVDs). ADAMTS17 overexpression in MG63 cells promoted extracellular microfibrils biogenesis, suggesting the potential role of ADAMTS17 in IVD function through interaction with fibrillin fibers. Finally, we provided evidence of FBN1 involvement in IVD function by showing that lumbar IVDs in patients with Marfan syndrome, caused by heterozygous FBN1 gene mutation, were significantly more degenerated. We identified a common SNP variant, located in ADAMTS17, associated with susceptibility to lumbar spondylosis and demonstrated the potential role of the ADAMTS17-fibrillin network in IVDs in lumbar spondylosis development.
(© 2023. The Author(s).)
Databáze: MEDLINE
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