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谷胱甘肽过氧化物酶 4 的遗传变异与子宫内膜异位症严重程度的关系。

Association between the Genetic Variants of Glutathione Peroxidase 4 and Severity of Endometriosis.

机构信息

Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, Taichung 40203, Taiwan.

Women's Health Research Laboratory, Changhua Christian Hospital, Changhua 50006, Taiwan.

出版信息

Int J Environ Res Public Health. 2020 Jul 15;17(14):5089. doi: 10.3390/ijerph17145089.

Abstract

It has been reported that oxidative and nitrative stress might be the pathogenesis of endometriosis. This prospective case-control study attempted to check the connection between single nucleotide polymorphism (SNP) of three antioxidant enzymes (glutathione peroxidase 4 (GPX4), thioredoxin 2 (TXN2), thioredoxin reductase 1 (TXNRD1)) and endometriosis. We recruited 90 patients with histology-approved endometriosis as the case group and 130 age-matched women for an annual pap smear examination as the control group. The stage of endometriosis was evaluated with revised ASRM score. Both groups were genotyped in the peripheral leukocytes for the SNP of GPX4 (rs713041), TXN2 (rs4821494) and TXNRD1 (rs1128446) by PCR-based methods. An X test was used to analysis of the difference of allele frequency and SNP distribution between two groups. The results revealed GPX4 (rs713041) has a significantly different distribution between two groups (C:T = 116 (44.6%):144 (55.4%) in control and C:T = 104 (57.8%): 76 (42.2%) in endometriosis groups, = 0.007). The SNP in TXN2 (rs4821494) also showed a difference in allele frequency (G:T = 180 (69.2%):80 (30.8%) in control and G:T = 141 (78.3%):39 (21.6%) in endometriosis group, = 0.030). In addition, the SNP GPX4 (rs713041) was associated with the severity of the endometriosis. Women who have advanced stage endometriosis were different from mild endometriosis in genetic variants of GPX4 gene ( = 0.001). In conclusion, the relationship between endometriosis and SNP of antioxidant enzymes, GPX4 and TXN2, was confirmed by the present study. According to the result, we suggested that the GPX4 might contribute to the pathogenesis of endometriosis.

摘要

据报道,氧化应激和硝化应激可能是子宫内膜异位症的发病机制。本前瞻性病例对照研究试图检查三种抗氧化酶(谷胱甘肽过氧化物酶 4 (GPX4)、硫氧还蛋白 2 (TXN2)、硫氧还蛋白还原酶 1 (TXNRD1))的单核苷酸多态性 (SNP)与子宫内膜异位症之间的关系。我们招募了 90 名经组织学证实的子宫内膜异位症患者作为病例组,以及 130 名年龄匹配的年度巴氏涂片检查妇女作为对照组。采用改良 ASRM 评分评估子宫内膜异位症的分期。两组均在外周白细胞中通过基于 PCR 的方法对 GPX4(rs713041)、TXN2(rs4821494)和 TXNRD1(rs1128446)的 SNP 进行基因分型。X 检验用于分析两组间等位基因频率和 SNP 分布的差异。结果表明,两组间 GPX4(rs713041)的分布有显著差异(对照组为 C:T=116(44.6%):144(55.4%),而子宫内膜异位症组为 C:T=104(57.8%):76(42.2%), = 0.007)。TXN2(rs4821494)的 SNP 也显示出等位基因频率的差异(对照组为 G:T=180(69.2%):80(30.8%),而子宫内膜异位症组为 G:T=141(78.3%):39(21.6%), = 0.030)。此外,GPX4(rs713041)的 SNP 与子宫内膜异位症的严重程度有关。患有晚期子宫内膜异位症的女性与轻度子宫内膜异位症在 GPX4 基因的遗传变异上存在差异( = 0.001)。总之,本研究证实了子宫内膜异位症与抗氧化酶、GPX4 和 TXN2 的 SNP 之间的关系。根据研究结果,我们认为 GPX4 可能有助于子宫内膜异位症的发病机制。

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