MnSOD、Catalase、UCP2、hOGG1、COMT和GSTM1基因多型性與子宮內膜異位症相關性之研究

Endometriosis is characterized by the implantation and growth of endometrial tissue outside the uterine cavity. The aetiological factor of endometriosis is still remain poorly understood. Somatic genetic alterations have been found in endometriotic lesions and these may contribute to initiation and progression of endometriosis. Approximately 85?90% of reactive oxygen species (ROS) generation was proposed during the mitochondrial electron transport chain. The intramitochondrial antioxidant enzymes play the pivotal role on the maintenance of mitochondrial genome integrity and intracellular normal function. In this study, we collected 122 infertile women and 48 normal fertile women. Women were divided into three groups: endometriosis (group A, n = 89), infertility patients (group B, n = 122) and normal control (group C, n = 48). The aim of this study was to test whether the manganese superoxide dismutase (MnSOD), catalase (CAT), uncoupling protein 2 (UCP), human 8-oxoguanine glycosylase 1 (hOGG1), catechol-O-methyltransferase (COMT), glutathione S-transferase M1 (GSTM1) polymorphisms and mtDNA T8993G mutation contributed to the risk of endometriosis pathogenesis. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were performed to analyze the genotype and genotype frequencies in the three groups and made statistic analysis by using chi-square test. In addition, we measured the content of 8-OHdG by HPLC-ECD detection and the occurrences of mtDNA deletions (4977 bp and 5756 bp) by long-PCR analysis. The frequency of the MnSOD CC+CT type was significantly higher in group A (25.1%:16.7%, p=0.02) and group B (33.6%:16.7%, p=0.029) compared with group C (16.7%). The proportion of catalase TT type was found higher in group A (25.1%:0%, p=0.029) compared group C (0%). Furthermore, the lower incidence of the hOGG1 CC genotype was observed in the patients with group A (15.7%:31.3%, p=0.034) and group B (15.6%:31.3%, p=0.021) compared with group C (31.3%). In addition, the hOGG1 CC genotype endometriotic tissues have lower 8-OHdG production than CG with GG genotype group (respectively 0.39±0.11 and 0.76±0.24 8-OHdG/105 dG, p=0.01). We supposed the C allele exhibited substantially the higher DNA repair activity than the CG variant and the G allele. No significant difference was found that the frequencies of UCP2, COMTLL, GSTM1 null type in cases and controls. Similarly, no association was observed in mtDNA T8993G mutation of endometriosis. In summary, hOGG1, MnSOD and CAT polymorphisms may play an important role in the risk for endometriosis. Our results suggest that the mitochondrial oxidative stress was related to the susceptibility of endometriosis and female infertility.