Tri-Service General Hospital Songshan Branch, National Defense Medical Center, Taipei 10581, Taiwan.
School of Public Health, National Defense Medical Center, Taipei 11490, Taiwan.
Genes (Basel). 2022 Jun 17;13(6):1084. doi: 10.3390/genes13061084.
Background: the impact of knee osteoarthritis (OA) poses a formidable challenge to older adults. Studies have reported that genetic factors, such as MMP1, are one of important risk factors for knee OA. Although the relationship between the genetic polymorphism of MMP1 rs1799750 and the risk of knee OA has been explored, conclusions have been nonunanimous and pending due to research sample sizes, one of determinants in studying genetic polymorphisms associated with disease. Objective: to establish a model to assess whether the genetic polymorphism of MMP1 rs1799750 is associated with knee OA based on an estimation of sample sizes. Methods: samples were collected from a case−control and meta-analysis study. In the case−control study, patients who underwent knee X-ray examinations based on the Kellgren−Lawrence Grading System (KL) as diagnostic criteria were recruited at the Health Examination Center of the Tri-Service General Hospital from 2015 to 2019. Gene sequencing was conducted using iPLEX Gold. Those with unsuccessful gene sequencing were excluded. Finally, there were 569 patients in the knee OA group (KL ≥ 2) and 534 participants in the control group (KL < 2). In the meta-analysis, we used the databases PubMed, EMBASE, and Cochrane to search for studies on the relationship between MMP1 rs1799750 and knee OA. Next, we adopted the trial sequential analysis (TSA) method to assess whether sample sizes were sufficient or not to determine the risk of the genetic polymorphism of MMP1 rs1799750 on knee OA in Caucasians and Asians. Results: in Caucasians, the MMP1 rs1799750 was not significantly associated with knee OA with an odds ratios (OR) of 1.10 (95% confidence interval, CI: 0.45−2.68). Some extra 8559 samples were needed to conclude this relationship in Caucasians by the TSA model. In Asians, neither our case−control study results (n = 1103) nor a combination of samples from the case−control and meta-analysis results showed an association between MMP1 rs1799750 and knee OA. The OR (95% CI) was 1.10 (0.81−1.49) in a combination of Asian samples. Some extra 5517 samples were needed to justify this relationship in Asians by the TSA model. Conclusions: this research shows that an extra 8559 and 5517 samples are needed in Caucasians and Asians, respectively, in order to justify the association between MMP1 rs1799750 and knee OA.
膝骨关节炎（OA）对老年人构成了巨大挑战。研究表明，遗传因素（如 MMP1）是膝 OA 的重要危险因素之一。尽管已经探讨了 MMP1 rs1799750 的遗传多态性与膝 OA 风险之间的关系，但由于研究遗传多态性与疾病相关的样本量是决定因素之一，因此结论尚未达成一致。目的：基于样本量估计，建立一种评估 MMP1 rs1799750 遗传多态性是否与膝 OA 相关的模型。方法：本研究采用病例对照和荟萃分析研究进行样本采集。在病例对照研究中，我们于 2015 年至 2019 年在三军总医院健康检查中心，招募了根据 Kellgren-Lawrence 分级系统（KL）进行膝关节 X 光检查的患者作为病例组。采用 iPLEX Gold 进行基因测序。对于那些基因测序不成功的患者，我们将其排除在外。最终，膝 OA 组（KL≥2）有 569 例患者，对照组（KL<2）有 534 例参与者。在荟萃分析中，我们使用 PubMed、EMBASE 和 Cochrane 数据库搜索 MMP1 rs1799750 与膝 OA 关系的研究。然后，我们采用试验序贯分析（TSA）方法评估 MMP1 rs1799750 遗传多态性对白人及亚洲人群膝 OA 风险的样本量是否充足。结果：在白人中，MMP1 rs1799750 与膝 OA 无显著相关性，比值比（OR）为 1.10（95%置信区间，CI：0.45-2.68）。TSA 模型显示，还需要额外 8559 个样本才能确定 MMP1 rs1799750 与白人膝 OA 之间的关系。在亚洲人群中，我们的病例对照研究结果（n=1103）和病例对照与荟萃分析结果的组合均未显示 MMP1 rs1799750 与膝 OA 之间存在关联。亚洲人群的 OR（95%CI）为 1.10（0.81-1.49）。TSA 模型显示，还需要额外 5517 个样本才能确定 MMP1 rs1799750 与亚洲人群膝 OA 之间的关系。结论：本研究表明，在白人及亚洲人群中，还需要额外 8559 个和 5517 个样本才能确定 MMP1 rs1799750 与膝 OA 之间的关系。
