PURPOSE Our aim was to evaluate the frequency and SNP-SNP interactions between factor V Leiden (FVL) G1691A, prothrombin G20210A mutation, and C677T MTHFR and PAI-1 4G/5G gene polymorphisms in female IVF patients with unexplained infertility (UI) by using a multifactor dimensionality reduction (MDR) model analysis. METHODS A total of 225 subjects were enrolled in the study. There were 105 females in UI group and 120 healthy controls. Designated SNPs were determined by using allele-specific PCR methods. The difference in thrombophilia prevalence was assessed by a chi-square test and logistic regression analysis. Four-locus SNP interaction model was tested using the MDR approach. A ten-fold cross-validation consistency (CVC) and permutation testing were performed. RESULTS There was a significant difference of MTHFR C677T polymorphism frequency between the groups. Significantly less UI patients had MTHFR CC genotype (p = 0.005), while the risk allele T was more frequent (OR = 1.83, p = 0.0018). Logistic regression determined a significant association only for MTHFR C677T in our patients (TT genotype OR = 2.99). The MDR analysis confirmed the significance of a single-locus model for MTHFR C677T polymorphism (p = 0.015; OR = 2.93). However, the best, significant predictive model was the two-locus model comprising MTHFR C677T and FVL (CVC = 10/10, testing accuracy = 60.95%, p = 0.013; OR = 3.02). CONCLUSION The MTHFR C677T polymorphism was significantly associated with UI, with minor allele T being more frequent. Additionally, there was a significantly increased presence of MTHFR C677T with FVL mutation in these patients. Therefore, MTHFR and its interaction with FVL should be recognized as contributing factors in the pathogenesis of infertility.

中文翻译：

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不明原因不孕症患者中易血栓性 SNP 的相互作用 - 多因素降维 (MDR) 模型分析。

目的 我们的目的是通过使用以下方法评估不明原因不孕症 (UI) 女性 IVF 患者中 V 因子 Leiden (FVL) G1691A、凝血酶原 G20210A 突变以及 C677T MTHFR 和 PAI-1 4G/5G 基因多态性之间的频率和 SNP-SNP 相互作用。多因素降维（MDR）模型分析。方法 共有 225 名受试者参加了该研究。UI组有105名女性和120名健康对照。通过使用等位基因特异性 PCR 方法确定指定的 SNP。通过卡方检验和逻辑回归分析评估血栓形成倾向患病率的差异。使用 MDR 方法测试四位点 SNP 相互作用模型。进行了十倍交叉验证一致性（CVC）和排列测试。结果 各组间MTHFR C677T多态性频率存在显着性差异。具有 MTHFR CC 基因型的 UI 患者明显较少 (p = 0.005)，而风险等位基因 T 则更为常见 (OR = 1.83，p = 0.0018)。Logistic 回归确定我们的患者中仅 MTHFR C677T 存在显着相关性（TT 基因型 OR = 2.99）。MDR 分析证实了 MTHFR C677T 多态性单基因座模型的重要性（p = 0.015；OR = 2.93）。然而，最好的显着预测模型是由 MTHFR C677T 和 FVL 组成的双基因座模型（CVC = 10/10，测试准确度 = 60.95%，p = 0.013；OR = 3.02）。结论 MTHFR C677T 多态性与 UI 显着相关，次要等位基因 T 更常见。此外，这些患者中具有 FVL 突变的 MTHFR C677T 的存在显着增加。因此，MTHFR 及其与 FVL 的相互作用应被认为是不孕症发病机制中的促成因素。