Medical Abortion Clinical Differences In Estrogen And Progesterone Receptor Gene Polymorphism

Nowadays, the mifepristone combined with misoprostol is an effective regimenfor termination of early pregnancy and is widely used in China. However, clinicalpractice indicates that there is diversity among the patients in the response to theregimen. Complete abortion rate is about 95 percent, incompletely abortion rate isabout 2～3precent and continuing pregnancy is about 1～2 percent. The days ofbleeding after abortion last for about 15～17days averagely, ranging between 4-60 days.There was heavy bleeding that account for 1 percent among patients of incompletelyabortion. Therefore, this method of medical abortion still needs to be improved.The reason for the diversity in response to mifepristone treatment is not clear yet.This may be attributed to combined effects of the environment and heredity. Thegenetic contribution to the variation of human in susceptibility to disease and drugresponse is nowadays drawing more and more attentions. Through study of theassociation of the SNP with the sensitivity of the regimen, the factor of heredity maybe revealed and thus can provide directions and basis for doctor in clinical.Accordingly, this research tries to utilize the concept, achievement and methods ofgenomics to search for the relationships of gene polymorphism and the differentmanifestations of mifepristone action among subjects, and approach the mechanism ofmedicine acting on target gene.Estrogen and progestogen are the most important hormones in women'sreproduction system. And estrogen and progestogen, which combine with theircognate receptor, produce a marked effect. Therefore, as transcriptive factors, estrogenreceptor and progestogen receptor play central roles in the control of target geneexpression. In the sequence of these genes encoding estrogen and progestogenreceptor, there are a lot of polymorphisms that may associate with the phenotype ofhormone response. Therefore, we are searching the association between single nuclearpolymorphism and sensitivity of medicine in abortion. We expect these efforts may disclose genetic basis for the diversity of response among abortion people. Thecontent of the study conclude extracting DNA of whole human blood, selecting thesites of the polymorphism, carrying out the experiment and statistics, and drawing asignificant conclusion.The subjects of this research mainly came from kuandian, beipiao and Liaoningfamily planning station and a total of approx. 1000 subjects were recruited to thestudy and samples from 165 subjects were selected for genetic analysis.Experiment methods: the subjects were divided into five groups according theirclinical phenotypes including fast responder of complete abortion, normal response ofcomplete abortion, incompletely abortion, abortion failure and prolonged bleeding.We choose one of the polymorphism sites of estrogen receptor and one mutation ofprogestogen receptor for examination. We adopt the main methods is PolymeraseChain Reaction and restriction fragment length polymorphism. The main techniqueroute is PCR-restricted enzyme cutting and DHPLC.Experiment result: the first experiment obtain three genotypes of AA (mutant),GG (wild) and AG (heterozygote) for rs2228480 site by restricted enzyme cutting theproduct of PCR. Utilized statistical software analysis, we found a regular change andgenotype distribution in the different manifestation of abortion people. The lowerincidence of AA genotype is more associated with faster responder and the higherincidence of GG genotype is associated with failure and incomplete abortion andprolonged bleeding. In other words: the more AA genotype, the better response to theregimen, and the more GG genotype, the worse response to the regimen. Itdemonstrate that there are close association between this polymorphism site ofestrogen receptorαgene and different manifestation of medical abortion people whoaccepted mifepristone plus misoprostol. In the second experiment, four subjects ofcontinuing pregnancy were analyzed together with 29 faster responders. We did notfind any mutation through sequencing in the fourth exon ofprogestogen receptor. Thisresult does not agree with the previous report that the existence of the mutation of the fourth exon of progesterone receptor in the subjects of continuing pregnancy.Our data provide significant information to investigate the genetic factors formedical abortion people, and may contribute to the prevention and treatment ofmedical abortion in clinical.