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

  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.