Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114201, Taiwan, R.O.C.
Department of Orthopedics, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan 330, Taiwan, R.O.C.
Aging (Albany NY). 2024 Sep 6;16(17):12346-12378. doi: 10.18632/aging.206094.
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.
To assess whether a definite conclusion of the association between the gene loci and OA can be drawn.
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 I value.
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.
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.
之前的荟萃分析仅研究了单个或多个基因多态性与骨关节炎（OA）之间的关联，而没有研究得出存在与 OA 相关的所有基因座的结论。
评估是否可以得出基因座与 OA 之间存在关联的明确结论。
使用基于文献的决定性基因策略（DGS）检索 PubMed、Embase 和 Cochrane 数据库中所有与基因多态性和 OA 相关的荟萃分析。试验序贯分析（TSA）检查累积样本量是否充足。最后，我们根据文献的异质性和样本量大小是否足够，使用 I 值评估基因座在 OA 中的重要性。
排除 179 篇不相关的文献后，共纳入 80 篇荟萃分析论文。在高加索人群中，SMAD3 rs12901499（OR=1.20，95%CI：1.12-1.29）是一个风险因素，通过 TSA 模型验证了样本量充足。在亚洲人群中，有 3 个基因座风险因素通过 TSA 模型验证了样本量充足：ESR1 rs2228480、SMAD3 rs12901499 和 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，分别）。此外，DVWA rs7639618、GDF5 rs143383 和 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，分别）通过 TSA 模型被确定为保护性因素。
我们使用 DGS 确定了与 OA 相关的明确的基因座。这些发现为 OA 的精准医学提供了启示，并可能为基因治疗提供潜在的进展。
