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芳香烃受体信号通路相关基因多态性及mRNA在子宫内膜异位症发病中的相互作用

Interaction between aromatic hydrocarbon receptor signaling pathway-related gene polymorphism and its mRNA in the development of endometriosis

    摘要
  • 摘要:
      目的  探讨芳香烃受体(AhR)信号通路相关基因AHR、AhR核异位蛋白(ARNT)、细胞色素P450 1A1(CYP1A1)、AhR阻遏蛋白(AhRR)、谷胱甘肽S转移酶1(GSTP1)、白细胞介素-1β(IL-1β)多态性及mRNA在子宫内膜异位症(EMT)发病中的相互作用。
      方法  选择手术病理确诊为EMT的25例患者为病例组, 25例非EMT患者为对照组。实时定量PCR法检测mRNA表达，定量PCR为基础的高分辨率熔解曲线(PCR-HRM)法检测基因多态性，采用单纯病例研究方法对基因-基因交互作用进行分析。
      结果  病例组中AhR mRNA、GSTP1 mRNA和IL-1β mRNA水平较对照组显著增高(P < 0.01)。病例组中ARNT mRNA水平显著高于对照组(P < 0.05)。携带CYP1A1 rs4646903 CC突变基因型的个体发生EMT的危险度是TT纯合野生型的7.5倍(95%CI: 1.29~43.69), 其他基因多态性的分布组间比较无显著差异(P>0.05)。CYP1A1 6235 T/C突变型与ARNT 522 G/C突变型(OR=9.33, 95%CI: 1.47~59.48)、GSTP1313 A/G突变型(OR=13.50, 95%CI: 1.34~135.98)存在协同作用。AHR 1661 G/A突变型与AHRR 565 C/G突变型存在协同作用(OR=13.50, 95%CI: 1.34~159.98), 其他基因位点未见交互作用。
      结论  携带CYP1A1 rs4646903 CC基因型的个体发生EMT的风险性较高, CYP1A1 6235 T/C与ARNT 522 G/C突变型间的联合作用以及CYP1A1 6235 T/C与GSTP1313 A/G突变型间的联合作用与EMT的发病有关。

     

    Abstract:
      Objective  To explore the interaction between aromatic hydrocarbon receptor (AhR) signaling pathway-related genes AHR, AhR nuclear heterotopic protein (ARNT), cytochrome P450 1A1 (CYP1A1), AhR repressor protein (AhRR), glutathione S-transferase 1 (GSTP1), interleukin-1β (IL-1β) polymorphism and messenger RNA (mRNA) in endometriosis pathogenesis (EMT).
      Methods  A total of 25 patients with endometriosis confirmed by surgery and pathology were selected as case group (n=25), and 25 non-EMT patients were selected as control group (n=25). Gene polymorphism were detected by Polymerase Chain Reaction-High Resolution Melt (PCR-HRM) method, and expressions of mRNA were detected by real-time quantitative PCR in both groups. The gene-gene interactions were analyzed based on the simple-case-study method.
      Results  The levels of AhR, GSTP1 and IL-1β mRNAs in case group were significantly higher than those in control group (P < 0.01). The level of ARNT mRNA in case group increased significantly when compared with that in control group (P < 0.05). The risk of EMT in patients with CYP1A1 rs4646903 CC mutation genotype was 7.5 times higher than patients with homozygous wild genotype TT (95%CI: 1.29 to 43.69), and there were no significant differences in frequencies of other genotypes between case group and control group (P>0.05). The synergistic role of mutated CYP1A1 6235 T/C and mutated ARNT 522 G/C gene increased the risk of endometriosis (OR=9.33, 95%CI: 1.47 to 59.48), and the risk of disease also increased when combined with mutated CYP1A1 6235 T/C and mutated GSTP1313 A/G gene (OR=13.50, 95%CI: 1.34 to 135.98). Moreover, combined with mutated AHR 1661 G/A and AHRR 565 C/G appeared to cause a significant increase in endometriosis (OR=13.50, 95%CI: 1.34 to 159.98). No interaction was found at other loci.
      Conclusion  Patients with CYP1A1 rs4646903 CC gene has a high risk in developing endometriosis. The combined mutated genotypes (CYP1A1 6235 T/C and ARNT 522 G/C, CYP1A1 6235 T/C and GSTP1313 A/G) might be related with susceptibility to endometriosis.

     

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