Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 11490, Taiwan.
Department of Family and Community Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan.
Genes (Basel). 2021 Mar 12;12(3):404. doi: 10.3390/genes12030404.
(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 (), which is widely studied to explore the gender difference in knee OA. Several polymorphisms in [PvuII (rs2234693) and BtgI (rs2228480)] were confirmed as the risk factors of OA. However, the evidence of the last widely investigated polymorphism, 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 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 XbaI and knee OA [OR: 0.78 (95% CI: 0.59-1.04)] with a high heterogeneity (: 78%). The result of Caucasians also concluded the null association [OR: 1.05 (95% CI: 0.56-1.95), : 87%]. (5) Conclusions: The association between XbaI and knee OA was not similar with other polymorphisms in , which is not a causal relationship. This study integrated all current evidence to elaborate this conclusion for suggesting no necessity of future studies.
(1) 背景：膝骨关节炎（OA）在女性中的患病率明显高于男性。由于其表达存在较大的性别差异，雌激素受体α（ERα）被认为发挥了关键作用。ERα 由基因雌激素受体 1（）编码，该基因被广泛研究以探索膝 OA 的性别差异。[PvuII（rs2234693）和 BtgI（rs2228480）]中的几个多态性已被确认为 OA 的危险因素。然而，对于最后一个广泛研究的多态性 Xbal（rs9340799），其对膝 OA 影响的证据仍不充分，不足以得出结论。(2) 目的：本研究提出了一项病例对照研究，以调查 Xbal 与膝 OA 之间的关联。此外，还进行了荟萃分析和试验序贯分析（TSA），以扩大样本量以获得更具结论性的证据。(3) 方法：总共招募了 497 例膝 OA 病例和 473 名健康对照者，时间为 2015 年 3 月至 2018 年 7 月。使用 Kellgren-Lawrence 分级系统来确定膝 OA 病例。为了提高本研究的证据水平，我们进行了荟萃分析，包括截至 2018 年 12 月从 PubMed、Embase 和先前的荟萃分析中发布的相关研究。结果表示为该多态性对膝 OA 风险的比值比（OR）及其相应的 95%置信区间（CI），以评估其影响。TSA 用于估计本研究中所需的样本量。(4) 结果：我们发现 G 等位基因与膝 OA 之间无显著关联[杂合模型中的粗 OR：0.97（95%CI：0.78-1.20）和调整 OR：0.90（95%CI：0.71-1.15）]，其他遗传模型的分析也显示出类似的趋势。在纳入六项已发表的研究和本病例对照研究后，目前有 3174 名亚洲人的证据表明 XbaI 与膝 OA 之间存在明确的无关性[OR：0.78（95%CI：0.59-1.04）]，异质性较高（：78%）。白种人的结果也得出了无关的结论[OR：1.05（95%CI：0.56-1.95），：87%]。(5) 结论：XbaI 与膝 OA 之间的关联与其他中的多态性不同，这不是因果关系。本研究综合了所有现有证据来阐述这一结论，建议无需进行进一步的研究。
