Relationship Between Endometriosis And Polymorphisms Of ACE And AT1R 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 displays some features of malignancy, including local invasion and aggressive spread to distant organs. Similar to tumour metastases, endometriotic implants require neovascul -arization to become established, grow and invade tissues. Neovascular processes are prominent in the endometric tissue. Angiogenesis and vascular remodelling play critical roles in the growth, invasion and regression of endometriosis. Heritable genetic factors may contribute to the initiation and progression of endometriosis. Cardiovascular genes play a role in the regulation and growth of tumour and altered vascular-related genes might be related to the development of endometriosis. The renin–angiotensin system (RAS) regulates blood pressure through its effects on vascular tone, renal haemodynamics and fluid–electrolyte balance. Circulating renin catalyzes the angiotensinogen-to-angiotensin I conversion. The angiotens -inogen gene is expressed in the liver, the site of AGT synthesis and release into the circulation. The angiotensin I (Ang I) generated by renin activity is a vasoinactive decapeptide. Conversion of angiotensin I to angiotensin II (Ang II) is the key reaction in the RAS pathway, generating the effector of the system, Ang II, a potent vasoconstrictor. The reaction is catalyzed by ACE, a zinc metallopeptidase member of the Alu family that functions as a dipeptidyl carboxypeptidase (DCP1) . The presence of angiotensin receptors has been demonstrated in the endometrial tissue. Angiotensin II in endometrial stromal cells was mediated via angiotensin I receptors. Angiotensin II could increase the intracellular calcium concentration by interaction with angiotensin receptor in endometrial stromal cells. Vasopressin also stimulates phospholipase C activity in endometrial explants. These findings suggest an underlying contribution of RAS for the development of endometrium and endometriosis. In this study, we aimed primarily to evaluate whether ACE A2350G, AT1RA1166C gene polymorphisms are attractive markers for moderate/severe endometriosis susceptibility.Methods: Group of patients with endometriosis: A total 78 women between 22 and 45 years old 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: 82 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 had normal blood pressure without obvious cardiovascular disease. The genomic DNA was prepared from peripheral blood leukocytes by the use of a genomic DNA isolation kit. The DNA was stored at -80oC until analyzed. ACE and AT1R fragment was amplified by polymerase chain reaction (PCR). After PCR amplification, the PCR products were digested at 37 oC with different restriction enzyme to detect the ACE and AT1R allele, then subjected to 8% PAGE 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 78 patients with stageⅢ,Ⅳendometriosis and 82 controls, proportions of ACE 2350*A homozygote/heterozygote /G homozygote were: 66.7/29.3/4% , and 96.2/3.1/0.7%, respectively (Χ2=12.041,P=0.01),OR=3.820(95%CI 1.745- 8.364 ) . Statistic analysis suggested ACE genotype polymorphism icreases risk ofⅢ,Ⅳendometriosis. The percentage of ACE 2350*A/G alleles in both groups were 81.3/18.7% and 97.8/2.2%, respectively (Χ2=10.616,P=0.01). OR= 3.227(95%CI 1.550-6.717)A statistic differences was found between the two groups. Statistic analysis suggested ACE 2350*G-related genotypes and alleles are associated with higher susceptibility to endometriosis. ACE A2350G gene polymorphisms might be associated withⅢ,Ⅳendometriosis development. 3 Proportions of AT1R-1166*A homozygote/ heterozygote/C homozygote in the group of endometriosis were: 66.7/29.3/4% , and in the control group were 96.2/3.1/0.7%, respectively(Χ2=0.128,P=0.721).OR=1.182(95%CI 0.472- 2.962). No association between AT1R polymorphisms andⅢ,Ⅳendometriosis was found. The percentage of AT1R 1166*A/C alleles in both groups were 81.3/18.7% and 97.8/2.2%, respectively(Χ2=0.119,P=0.823). OR=1.168 ( 95%CI 0.482- 2.833)No differences was also found between the two groups. This indicated that AT1R gene polymorphism may not be an independent risk factor in endometriosis development.Conclusion: 1 These results suggest that the ACE polymorphism may contribute to the genetic influence on stageⅢ,Ⅳendometriosis. 2 There was no association between AT1R polymorphism and stageⅢ,Ⅳendometriosis.