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Abstract：
(1) Background: The prevalence of knee osteoarthritis (OA) in women is significantly higher than in men. The estrogen receptor α (ERα) has been considered to play a key role due to a large gender difference in its expression. ERα is encoded by the gene estrogen receptor 1 (ESR1), which is widely studied to explore the gender difference in knee OA. Several polymorphisms in ESR1 [PvuII (rs2234693) and BtgI (rs2228480)] were confirmed as the risk factors of OA. However, the evidence of the last widely investigated polymorphism, ESR1 Xbal (rs9340799), is still insufficient for concluding its effect on knee OA. (2) Objective: This study proposed a case-control study to investigate the association between ESR1 Xbal and knee OA. Moreover, a meta-analysis and trial sequential analysis (TSA) were conducted to enlarge the sample size for obtaining a conclusive evidence. (3) Methods: In total, 497 knee OA cases and 473 healthy controls were recruited between March 2015 and July 2018. The Kellgren-Lawrence grading system was used to identify the knee OA cases. To improve the evidence level of our study, we conducted a meta-analysis including the related studies published up until December 2018 from PubMed, Embase, and previous meta-analysis. The results are expressed as odds ratios (ORs) with corresponding 95% confidence intervals (CI) for evaluating the effect of this polymorphism on knee OA risk. TSA was used to estimate the sample sizes required in this issue. (4) Results: We found non-significant association between the G allele and knee OA [Crude-OR: 0.97 (95% CI: 0.78-1.20) and adjusted-OR: 0.90 (95% CI: 0.71-1.15) in allele model] in the present case-control study, and the analysis of other genetic models showed a similar trend. After including six published studies and our case-control studies, the current evidence with 3174 Asians showed the conclusively null association between ESR1 XbaI and knee OA [OR: 0.78 (95% CI: 0.59-1.04)] with a high heterogeneity (I2: 78%). The result of Caucasians also concluded the null association [OR: 1.05 (95% CI: 0.56-1.95), I2: 87%]. (5) Conclusions: The association between ESR1 XbaI and knee OA was not similar with other polymorphisms in ESR1, which is not a causal relationship. This study integrated all current evidence to elaborate this conclusion for suggesting no necessity of future studies.
摘要：
(1)背景:女性膝关节骨性关节炎(OA)患病率明显高于男性。雌激素受体α（ERα）由于其表达的性别差异很大，因此被认为起着关键作用。ERα由雌激素受体1（ESR1）基因编码，这是广泛的研究，以探讨膝关节OA的性别差异。ESR1[PvuII(rs2234693)和BtgI(rs2228480)]中的一些多态性被证实是OA的危险因素。然而,最后广泛研究的多态性的证据，ESR1Xbal(rs9340799),仍然不足以得出其对膝关节OA的影响。（2）目的：本研究提出了一项病例对照研究，以探讨ESR1Xbal与膝关节OA之间的关系。此外，我们进行了荟萃分析和试验序贯分析(TSA),以扩大样本量,从而获得结论性证据.(3)方法：总的来说，在2015年3月至2018年7月之间招募了497例膝OA病例和473名健康对照。Kellgren-Lawrence分级系统用于识别膝关节OA病例。为了提高我们研究的证据水平，我们进行了一项荟萃分析，包括截至2018年12月从PubMed发表的相关研究，Embase,和以前的荟萃分析。结果表示为比值比(OR)和相应的95%置信区间(CI),用于评估该多态性对膝OA风险的影响。TSA用于估计本期所需的样本量。（4）结果：在本病例对照研究中，我们发现G等位基因与膝关节OA[粗OR：0.97（95％CI：0.78-1.20）和校正OR：0.90（95％CI：0.71-1.15）]之间无显着关联。和其他遗传模型的分析也显示出类似的趋势。在包括六项已发表的研究和我们的病例对照研究之后，目前有3174名亚洲人的证据显示,ESR1XbaI与膝关节OA[OR:0.78(95%CI:0.59-1.04)]之间存在明显的零相关性,且具有高度异质性(I2:78%).高加索人的结果也得出结论为零关联[OR：1.05（95％CI：0.56-1.95），I2:87%]。(5)结论:ESR1XbaI与膝关节OA的关联与ESR1的其他多态性不相似,不存在因果关系。这项研究综合了所有现有证据来阐述这一结论，表明没有必要进行未来的研究。
