Abstract：
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.
摘要：
背景：膝骨关节炎（OA）的影响对老年人构成了巨大的挑战。研究报告说，遗传因素，MMP1等是膝关节OA的重要危险因素之一。虽然MMP1rs1799750基因多态性与膝关节OA风险之间的关系已被探讨,由于研究样本量的原因，结论一直不一致，悬而未决，研究与疾病相关的遗传多态性的决定因素之一。目的:基于样本量估计,建立MMP1rs1799750基因多态性与膝关节OA是否相关的模型。方法：样本来自病例对照和荟萃分析研究。在病例-对照研究中，2015-2019年,在三军总医院健康检查中心招募了以Kellgren-Lawrence分级系统(KL)为诊断标准进行膝关节X线检查的患者.使用iPLEXGold进行基因测序。排除基因测序不成功的那些。最后,膝关节OA组569例(KL≥2),对照组534例(KL<2).在荟萃分析中，我们使用了PubMed数据库，EMBASE,和Cochrane寻找MMP1rs1799750与膝关节OA关系的研究。接下来,我们采用试验序贯分析(TSA)方法评估样本量是否足以确定高加索人和亚洲人MMP1rs1799750基因多态性在膝OA中的风险.结果：在高加索人中，MMP1rs1799750与膝关节OA无显著相关,比值比(OR)为1.10(95%置信区间,CI：0.45−2.68）。需要额外的8559个样本才能通过TSA模型在高加索人中得出这种关系。在亚洲人中，我们的病例-对照研究结果(n=1103)以及病例-对照样本和荟萃分析结果均未显示MMP1rs1799750与膝关节OA之间存在关联.在亚洲样品的组合中,OR(95%CI)为1.10(0.81-1.49)。通过TSA模型，需要额外的5517个样本来证明亚洲人的这种关系。结论：这项研究表明，高加索人和亚洲人需要额外的8559和5517个样本，分别,为了证明MMP1rs1799750与膝关节OA之间的相关性。
