Two GWAS-identified variants are associated with lumbar spinal stenosis and Gasdermin-C expression in Chinese population

Abstract

The aim of this study is to investigate the expression levels of genome-wide association studies (GWAS)-identified variants near Gasdermin-C (GSDMC) and its association with lumbar disc degeneration (LDD) in a Chinese population. In accordance with previously reported findings, our study involved the top 4 variants; rs6651255, rs7833174, rs4130415, and rs7816342. A total of 800 participants, 400 LDD patients and 400 controls were involved in the study. The LDD patients were divided into two mutually exclusive subgroups: subgroup 1: lumbar disc herniation; subgroup 2: lumbar spinal stenosis. Genotyping were performed using TaqMan assay, and Enzyme-Linked Immunosorbent Assay (ELISA) used to measure the plasma GSDMC levels, while quantitative reverse-transcription (qRT)-PCR and immunohistochemistry (IHC) were used to evaluate the GSDMC expression levels. Among the studied variants, there were no statistically significant differences in allelic and genotypic frequencies between LDD patients and their controls (all P > 0.05). However, the subgroup analysis revealed a significant association between rs6651255 and rs7833174 in patients with lumbar spinal stenosis (subgroup 2). Furthermore, the max-statistic test revealed that the inheritance models of two variants of lumbar spinal stenosis were represented by the recessive model. The plasma and mRNA expression levels of GSDMC were significantly higher in patients with lumbar spinal stenosis compared with the control group (P < 0.05). Furthermore, the CC genotypes of rs6651255 and rs7833174 were significantly associated with increased plasma expression levels of GSDMC in patients with lumbar spinal stenosis (P < 0.01). Two GWAS-identified variants (rs6651255 and rs7833174) near GSDMC were associated with a predisposition to lumbar spinal stenosis. GSDMC protein and mRNA expression levels may have prognostic qualities as biomarkers for the existence, occurrence or development of lumbar spinal stenosis.

The origins and spread of domestic horses from the Western Eurasian steppes

“…The presence of additional exons in other mammals suggests that independent L1 insertions remodelled the DOM2 gene structure. In humans, GSDMC is a strong marker for chronic back pain 29 and lumbar spinal stenosis, a syndrome causing vertebral disk hardening and painful walking 30 .…”

Pyroptosis, metabolism, and tumor immune microenvironment

“…125,155 Ultraviolet irradiation can induce the expression of GSDMC mediated by the calcium/calcineurin/nuclear factor of activated T-cells, the cytoplasmic 1 (NFATc1) pathway and the extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK)/matrix metalloproteinase 1 pathway in human skin keratinocytes. 156,157 Genomewide association studies show that GSDMC is associated with chronic back pain, 158 Mycoplasma hyopneumoniae (M. hyo) Ab variations in pigs, 159 lumbar spinal stenosis, 122 multi-type methylation in subchondral bone cartilage and osteoarthritis-related cartilage, 160,161 sciatica derived from lumbar disc herniation, 162 and monocyte counts. 163 GSDMC functions as an oncogene, mediating varieties of progressive processes involving types of tumors.…”

Low Back Pain With Persistent Radiculopathy; the Clinical Role of Genetic Variants in the Genes SOX5, CCDC26/GSDMC and DCC

“…The present study did not support the hypothesis that the SNP rs7833174 located between CCDC26 and GSDMC is associated with LBP with radiculopathy 12 months after an acute episode of LBP with radiculopathy. However, CCDC26 / GSDMC rs7833174 have been associated with lumbar microdiscectomy ( Bjornsdottir et al, 2017 ) and lumbar spinal stenosis ( Jiang et al, 2020 ), and a different variant GSDMC rs77681114 have been associated with lumbar disc herniation ( Wu et al, 2020 ). Lumbar micro discectomy is a common treatment for lumbar disc herniation ( Schoenfeld and Weiner, 2010 ) and both lumbar disc herniation and lumbar spinal stenosis may cause radiculopathy ( Konstantinou and Dunn, 2008 ).…”