Relationship Between Endometriosis And Polymorphisms Of CYP17,CYP1A2,CYP3A4 And COMT Gene

Objictive: Endometriosis(EMs) is a common gynecolo -gical disease of reproductive-aged women. The cause of EMs remains obscure. The results of epidemiological family studies and environmental investigations mean endomtriosis can be considered as a multifactorial disease with a possible genetic predisposition and with the involvement of environmental toxins. Endometriosis has hereditary basis and family gather incline,thereby Endometriosis has inheritance susceptibility,namely interpersonal individual gene difference makes individual susceptibility different.There are lot of researchs about endometriosis and polymorphism, for instance estrogen receptor, conformity white, inflammatory factor, matrix metalloproteinases.Endometriosis is a estrogen dependent- disease . Heterotopia endometrium generable estrogen , function through the medium of estrogen receptor .Ems may be association with estrogen-metabolizing gene , multi- environmental factor induce EMS, maybe singl genic- be unable to induce EMs,genic polymorphism impact enzyme activity, the difference could play role to individual who susceptibility to EMS. The synthesize and metabolism E by different enzyme , CYP17 is the E synthesize mesne key enzyme ,CYP1A2, CYP3A4, and COMT are key enzyme of metabolism E .Wherefore, CYP17,CYP1A2,CYP3A4 COMT are the candidate for pathopoiesis to EMS. So, it is necessary research the polymorphism of CYP17,CYP1A2 CYP3A4,COMT at the pepole, illuminate the ralation of E and EMS. These try consist research cyp1A2 gene G-2964A, CYP3A4 gene A-290G, COMT gene G1947A, CYP17 gene T-34C gene polymorphism and inside strange disease 'inheritance susceptibility' relation out.In this study, we aimed primarily to evaluate whether CYP17 gene T-34C, CYP1A2 gene G-2964A,CYP3A4 gene A-290G and COMT gene G1947A gene polymorphisms are attractive markers for moderate/severe endometriosis susceptibility.Methods: Group of patients with endometriosis: A total 108 women undergoing laparotomy or laparoscopy for endometriosis in the Department of Obstetrics and Gynecology of the Second Affiliated Hospital of Hebei Medical University. Diagnosis of endometriosis was establishied laparoscopically and histologically. In clinical practice, most women with minimal/mild endometriosis accept conservative medication instead of invasive management. Therefore, we only recruited the moderate/severe endometriosis women for the survey. Control group: 84 women were from non-endometriosis patients who were such conditions as reananstomosis infertility or ovarian dysembryoma or simple cyst, and without pelvic endometriosis and adenomyosis and adenomyosis evidenced by laparotomy or laparoscopy, with no history of endometriosis. All patients did not oral estrogen without estrogen dependent disease. The genomic DNA was prepared from peripheral blood leukocytes by the use of a genomic DNA isolation kit. The DNA was stored at -80℃until analyzed. CYP17,CYP1A2,CYP3A4 and COMT fragment was amplified by polymerase chain reaction (PCR). After PCR amplification, the PCR products were digested at 37℃with different restriction enzyme to detect the CYP17,CYP1A2,CYP3A4 and COMT allele, then subjected to 2% or 3% agarose gel electrophoresis and visualized under ultraviolet light. Statistical analysis was performed using SPSS13.0 software package. Two-tailed test with P<0.05 were considered significant.Results: 1 Hardy-Weinberg analysis was performed to compare the observed and expected genotype frequencies using Chi-square test, finally shows P>0.05, indicated in choosing the community the candidate gene has reached the heredity balance. 2 Among 108 patients with stageⅢ,Ⅳendometriosis and 84 controls, proportions of CYP17 -34T homozygote/heterozygote /C homozygote were: 25.9/47.2/26.9% , and 10.7/47.6/41.7%, respectively (χ~2=8.786,P=0.012),OR=0.514(95%CI 0.280～0.944 ) . Statistic analysis suggested CYP17 genotype polymorphism icreases risk ofⅢ,Ⅳendometriosis. The percentage of CYP17 -34*T/C alleles in both groups were 49.5/50.5% and 34.5/65.5%, respectively (χ~2=8.692,P=0.003). OR= 0.537(95%CI 0.355～0.813)T statistic differences was found between the two groups. Statistic analysis suggested CYP17 -34*T related genotypes and alleles are associated with higher susceptibility to endometriosis. CYP17 T-34C gene polymorphisms might be associated withⅢ,Ⅳendometriosis development. 3 Proportions of CYP1A2 -2964*G homozygote/ heterozygote/A homozygote in the group of endometriosis were: 56.5/38.0/5.5% , and in the control group were 64.3/28.6/7.1%, respectively(χ~2=1.902,P=0.386).OR=1.183 95%CI 0.738～1.894). No association between CYP1A2 polymorphisms andⅢ,Ⅳendometriosis was found. The percentage of CYP 1A2 -2964*G/A alleles in both groups were 75.5/24.5% and 78.6/21.4%,respectively(χ~2=0.513,P=0.474).OR=1.192(95% CI 0.737～1.930)No differences was also found between the two groups. This indicated that CYP1A2 gene polymorphism might not be an independent risk factor in endometriosis development. Compared with G/A+A/A genotypes ,the G/G could not increased the risk of developing endometriosis,χ~2= 1.198,P= 0.274,the OR=0.721(95%CI= 0.401～1.296)。4 the group of endometriosis and control are not any A-290G mutation of CYP3A4. 5 Proportions of COMT 1947*G homozygote/ heterozygote/A homozygote in the group of endometriosis were: 63.9/34.2/1.9% , and in the control group were 58.3/32.1/9.5%, respectively(χ2=5.640,P=0.06 ) . No association between COMT polymorphisms andⅢ,Ⅳendometriosis was found. The percentage of COMT 1947*G/A alleles in both groups were 81.0/19.0% and 74.4/25.6%, respectively(χ~2=2.419, P=0.120 ). No differences was also found between the two groups. This indicated that COMT gene polymorphism may not be an independent risk factor in endometriosis development. Compared with G/A+A/A genotypes ,the G/G could not increased the risk of developing endometriosis,χ~2= 0.616,P= 0.433,the OR = 1.264(95%CI= 0.704～2.269).Conclusion:1 These results suggest that the CYP17 T -34C polymorphism may contribute to the genetic influence on stageⅢ,Ⅳendometriosis,carrying CYP17*T genotype could be associated with the increased risk of developing stageⅢ,Ⅳendometriosis.2 There was no association between CYP1A2 G-2964A polymorphism and stageⅢ,Ⅳendometriosis.3 there are not any A-290G mutation of CYP3A4.4 The COMT G1947A polymorphism might not be related to the risk of stageⅢ,Ⅳendometriosis development.