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Research Paper|Volume 16, Issue 17|pp 12346—12378

Decisive gene strategy on osteoarthritis: a comprehensive whole-literature based approach for conclusive gene targets

Yi-Chou Chen1,2, Yu-Chiao Wang3, Meng-Chang Lee3, Yu-Hsuan Chen3, Wen Su4, Pi-Shao Ko5, Cheng-Jung Chen6,7, Sui-Lung Su1,3
  • 1Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114201, Taiwan, R.O.C
  • 2Department of Orthopedics, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan 330, Taiwan, R.O.C
  • 3School of Public Health, National Defense Medical Center, Taipei 114201, Taiwan, R.O.C
  • 4Graduate Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Taipei 114201, Taiwan, R.O.C
  • 5Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114201, Taiwan, R.O.C
  • 6Division of General Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 114202, Taiwan
  • 7Department of Surgery, Chiayi Branch, Taichung Veterans General Hospital, Chiayi City 60090, Taiwan
Received: January 2, 2024Accepted: August 2, 2024Published: September 6, 2024
https://doi.org/10.18632/aging.206094

Copyright: © 2024 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: Previous meta-analyses only examined the association between single or several gene polymorphisms and osteoarthritis (OA), whereas no studies have concluded that there are existing all gene loci that associate with OA.

Objective: To assess whether a definite conclusion of the association between the gene loci and OA can be drawn.

Methods: Decisive gene strategy (DGS), a literature-based approach, was used to search PubMed, Embase, and Cochrane databases for all meta-analyses that associated gene polymorphisms and OA. Trial Sequential Analysis (TSA) examined the sufficiency of the cumulative sample size. Finally, we assessed the importance of gene loci in OA based on whether there were enough sample sizes and the heterogeneity of the literatures with I2 value.

Results: After excluding 179 irrelevant publications, 80 meta-analysis papers were recruited. Among Caucasians, SMAD3 rs12901499 (OR = 1.20, 95% CI: 1.12-1.29) was a risk factor with validation of sufficient sample sizes through TSA model. Among Asians, there were 3 gene loci risk factors with validation of sufficient sample sizes through TSA model: ESR1 rs2228480, SMAD3 rs12901499, and MMP-1 rs1799750 (OR = 1.35, 95% CI: 1.08-1.69; OR = 1.34, 95% CI: 1.07-1.69; OR = 1.43, 95% CI: 1.18-1.74, respectively). Besides, 3 gene loci, DVWA rs7639618, GDF5 rs143383, and VDR rs7975232 (OR = 0.78, 95% CI: 0.67-0.90; OR = 0.74, 95% CI: 0.67-0.81; OR = 0.56, 95% CI: 0.35-0.90, respectively) were identified as protective factors through TSA model.

Conclusions: We used DGS to identify conclusive gene loci associated with OA. These findings provide implications of precision medicine in OA and may potentially advance genetic therapy.