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Effects of circulating inflammatory proteins on spinal degenerative diseases: Evidence from genetic correlations and

Qingcong Zheng1, Rongjie Lin2, Du Wang3

  • 1Department of Spinal Surgery The First Affiliated Hospital of Fujian Medical University Fuzhou China.

JOR Spine
|June 19, 2024
PubMed

Insights

This study investigated causal links between circulating inflammatory proteins (CIPs) and spinal degenerative diseases (SDDs). Several CIPs were found to increase the risk of cervical spondylosis, disc prolapse, spinal stenosis, and spondylolisthesis.

Area of Science:

  • Genetics
  • Immunology
  • Orthopedics

Background:

  • Spinal degenerative diseases (SDDs) are common, with suspected links to circulating inflammatory proteins (CIPs).
  • Causality between CIPs and SDDs remains unproven.
  • Investigating these links can elucidate disease mechanisms and identify therapeutic targets.

Purpose of the Study:

  • To investigate the causal associations between 91 CIPs and four common SDDs using Mendelian randomization.
  • To identify specific CIPs that causally influence the risk of cervical spondylosis (CS), prolapsed disc/slipped disc (PD/SD), spinal canal stenosis (SCS), and spondylolisthesis/spondylolysis.

Main Methods:

  • Utilized genome-wide association studies (GWAS) data for genetic variants of CIPs and SDDs.
  • Employed Mendelian randomization (MR), with inverse variance weighted (IVW) as the primary analysis method.
  • Performed pleiotropy and heterogeneity tests for robustness and reverse MR analysis to assess reverse causality.

Main Results:

  • Identified causal effects of specific CIPs on SDD risk, including beta-nerve growth factor (β-NGF), CXCL6, and IL-6 for CS.
  • Found FGF19, SULT1A1, and TNF-β associated with increased PD/SD risk, while u-PA showed a decreased risk.
  • Revealed FGF19 and TNF linked to increased SCS risk, and STAMBP and CD6 isoform linked to increased spondylolisthesis/spondylolysis risk, with MCP2 and LAP-TGF-β1 showing decreased risk.

Conclusions:

  • Established causal associations between multiple genetically predicted CIPs and the risk of four major SDDs.
  • Provided reliable genetic evidence supporting the role of CIPs in the pathogenesis of SDDs.
  • Highlighted novel potential therapeutic targets for SDDs based on identified CIPs.
Abstract

Keywords:
Mendelian randomizationcervical spondylosiscirculating inflammatory proteinsprolapsed disc/slipped discspinal canal stenosisspinal degenerative diseasesspondylolisthesis/spondylolysis

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