Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Taniguchi Y

PROVIDER: S-EPMC10039864 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Taniguchi Yuki Y Akune Toru T Nishida Nao N Omori Go G Ha Kim K Ueno Kazuko K Saito Taku T Oichi Takeshi T Koike Asako A Mabuchi Akihiko A Oka Hiroyuki H Muraki Shigeyuki S Oshima Yasushi Y Kawaguchi Hiroshi H Nakamura Kozo K Tokunaga Katsushi K Tanaka Sakae S Yoshimura Noriko N

Scientific reports 20230325 1

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 ADAMTS1 ...[more]

PMID: 36966180

Similar Datasets

Project description:BackgroundLow back pain from lumbar spondylosis affects a large proportion of the population. In select cases, lumbar fusion may be considered. However, cohort studies have not shown clear differences in long-term outcomes between PSF, TLIF, ALIF, and AP fusion. Thus, differences in perioperative complications might affect choice between these procedures for the given diagnosis. The current study seeks to compare perioperative adverse events for patients with lumbar spondylosis treated with single-level: posterior spinal fusion (PSF), transforaminal lumbar interbody fusion (TLIF), anterior lumbar interbody fusion (ALIF), or combined anterior and posterior lumbar fusion (AP fusion).MethodsPatients with a diagnosis of lumbar spondylosis who underwent single-level lumbar fusion without decompression were identified in the 2010-2016 National Quality Improvement Program (NSQIP) database. Patients were categorized based on their procedure (PSF, TLIF, ALIF, or AP fusion). Unadjusted Fisher's exact and Pearson's chi-squared tests were used to compare demographics and comorbid factors. Analysis was secondarily done with propensity score matching to address potential differences in patient selection between the study cohorts.ResultsIn total, 1816 patients were identified: PSF n=322, TLIF n=800, ALIF n=460, AP fusion n=234. The procedures did not have different thirty-day individual or aggregated (any, serious, minor, or infection) adverse events. Further, propensity score matched analysis also revealed no differences in individual or aggregated thirty-day perioperative events.ConclusionThe current study demonstrates a lack of difference in thirty-day perioperative adverse events for different fusion procedures performed for lumbar spondylosis, consistent with prior longer-term outcome studies. These findings suggest that patient/surgeon preference and other factors not captured here should be considered to determine the best surgical technique for the select patients with the given diagnosis who are considered for lumbar fusion.Summary sentenceUsing the NSQIP 2010-2016 databases, this study showed that perioperative adverse events were similar for different surgical approaches of single-level fusion for single-level lumbar spondylosis.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets