Associations P27 Gene Polymorphism And Its Protein Production With Endometriosis

Background:Endometriosis is a hormonal dependent,polygenic multi-factorial and hemorrhagic disease that affects 10% to 15% of women of reprodutive age. This disease can bring chonic pelvic pain and infertility for women.In the past few decades several aspects of endometriosis have been comprehensively discussed,but the exactly mechanisms of the disease remain unknown.Among the several pathogenetic theorise,Sampson's theory of retrograde menstruation is the most commonly accepted one.However,the theory can not explain why the disease appears in only some women with retrograde menstruation.Recent years,Professor Lang Jinghe proposed a new theory to EMs,the "Abnormal Eutopic Endometrium Theory".According to this theory,the main factor to the susceptibility to EMs is the abnormal adherence,aggression and angiogenesis potential of the eutopic endometrium.The theory is a very improtant revisal to the retrograde menstruation theory.P27 protein is a cyclin-dependent kinase inhibitor, it negatively regulates transition from Gl to S phase of cell cycle, by suppressing the activity of CDK complexes.It is supposed to be a tumor suppressor gene.It is observed that the P27 gene polymorphism was found in many human cancers.And a decreased level of P27 protein expression has been dete-cted in ovarian,endometrial,breast neoplasia and cancer of prostate.In the present study,first,we attempt to evaluate P27 protein expression in the endometrium of women with endometriosis.And then, investigate the prevalence of the P27 gene polymorphism in women with endometriosis.Methods:1.Detect P27 protein expression of cultured EMs eutopic endometrial cells by flow cytometry. At the same time,the expression of P27 protein determined by SP immunohistochemistry in 38 cases of ectopic endometrium of EMs,in 38 cases of eutopic endometrium of EMs and in 22 eutopic endometrium of control women without EMs.Analyzing the expression of P27 exprotein through Pearson chi-square test,Fisher'S exact test and Spearman correlations.2.The polymorphic variant at codon 109 of P27 gene was investigated using the polymerase chain reaction restriction frament length polymorphism(PCR-RFLP) method in a population that including 101 women with surgically confirmed EMs and 110 women from non-endometriosis patients.Statistical analysis was performed using SPSS16.0 software package. Two-tailed test with P<0.05 were considered significant.Results:1.The level of P27 protein expression observed in the EMs group,both in vitro cells and in endometrial biopsies,was significantly different from that observed in the control groups.The P27 protein expressed in nucleus of glandular epithelium.The level of P27 protein in proliferative phase was lower than secretory phase in eutopic endometrium.The P27 protein express significanthly higher in eutopic endometrium without EMs than ectopic endometrium of EMs and eutopic endometrium of EMs.2.The distribution of genotype and allele frequencies of P27 109V/G was different between the EMs cases and control women without EMs (p<0.005).Women that had at least one G(VG/GG) allele had more chances for EMs development.Conclusion:1.The decrease level of P27 protein in vitro cells and tissues of EMs suggests that cell cycle alterations may be involved in the pathogenesis of EMs.2.The distribution of genotype and allele frequencies of P27 109V/G maybe arelated with more chances for EMs development.