Association of ADAMTS4 and ADAMTS5 polymorphisms with musculoskeletal degenerative diseases: a systematic review and meta-analysis

Biosci Rep. 2018 Nov 30;38(6):BSR20181619. doi: 10.1042/BSR20181619. Print 2018 Dec 21.

Abstract

Objective: This meta-analysis and systematic review was performed with the aim of investigating the association between a disintegrin and metalloproteinase with thrombospondin motif (ADAMTS)4, AMDMTS5 polymorphisms and risk of musculoskeletal degenerative diseases.

Methods: PubMed, EMBASE, ISI Web of Science, Wanfang and CNKI were searched from their inception until May 2018 to identify eligible studies. Data from individual studies were extracted using a standardized data collection sheet. The estimate of association between ADAMTS4, AMDMTS5 polymorphisms and risk of musculoskeletal degenerative diseases was expressed as odds ratio (OR) along with its related 95% confidence interval (95%CI) under an allelic model of inheritance. Meta-analysis was conducted using RevMan 5.3 software. Subgroup-analyses by ethnicity and type of diseases were performed.

Results: Eight studies including ten cohorts were included in this meta-analysis. The meta-analyses results based on seven studies showed that rs226794 in ADAMTS5 gene was not associated with risk of musculoskeletal degenerative diseases (A vs. G: OR 1.07; 95%CI 0.97-1.19; P=0.16). Rs2830585 in ADAMTS5 was significantly associated with musculoskeletal degenerative diseases in only Asians (OR 1.41, 95%CI 1.18-1.68; P=0.0001), but not in Caucasians. Since only two of the collected studies referred to ADAMTS4, we did not perform meta-analysis for these comparisons.

Conclusion: Taken together, rs226794 and rs2830585 in ADAMTS5 gene were not associated with musculoskeletal degenerative diseases in overall population, but there seemed to be an ethnicity-dependent effect of rs2830585 in the risk of musculoskeletal degenerative diseases. Insufficient evidence was found to support the association of other single nucleotide polymorphisms and musculoskeletal degenerative diseases.

Keywords: ADAMTS4; ADAMTS5; lumbar disc degeneration; meta analysis; osteoarthritis; single nucleotide polymorphisms.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • ADAMTS4 Protein / genetics*
  • ADAMTS5 Protein / genetics*
  • Alleles
  • Asian People / genetics
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • Musculoskeletal Diseases / genetics*
  • Musculoskeletal Diseases / physiopathology
  • Polymorphism, Single Nucleotide / genetics
  • White People / genetics

Substances

  • ADAMTS5 Protein
  • ADAMTS5 protein, human
  • ADAMTS4 Protein
  • ADAMTS4 protein, human