Study On The Relationship Between The COX-2and Genetic Polymorphism And Pain Related To EMs

Objective: To determine the serumal cyclooxygenase-2(COX-2) level inendometriosis (EMs) patients and assess its correlation with the pain of EMs;Toinvestigate the genotype distribution of the COX-2gene and the relationship betweenpolymorphism of the COX-2gene and EMs and the pain related to EMs; Further to testthe correlation with COX-2genetic polymorphism and the serum COX-2level;To findthe cause of pain molecular intervention role site, can provide theoretical basis for thetreatment of EMs pain.Methods:60patients with EMs were recuited from DaLian Maternity Hospitalbetween June2010and May2011.All the patients were diagnosed as ovarian cystendometrial samples and confirmed by histology. EMs was staged according to theAmerican Fertility Society(r-AFS) classification.Groups of patients with EMs wereIII~IV.We divided these cases into pain group32cases and non-pain group28cases.The EMS with pain group was recorded the level of pain using VAS evaluation.10cases into mild pain group(1~3scores),10cases into moderate pain group(4~6scores)and12cases into severe pain group(7~10scores).Control group:29healthywomen were selected from outpatient service and had non-endometriosis.2ml ofvenous blood from each subject was drawn and stored at-70℃until analyzed.SerumCOX-2levels of patients with EMs with pain,without pain and healthy control groupswere determined by enzyme linked-immunosorbent assay(ELISA).Genotypes ofCOX-2-1195and COX-2-765of all groups were determined by polymerase chainreaction-based restriction fragment length polymorphism(PCR-RFLP).Statisticalanalysis was performed using SPSS17.0software package.Two-tailed test with P<0.05were considered significant.Results:1.The serum COX-2level of EMs pain group was obviously higher than those of control and EMs without pain group,and there was no difference betweencontrol and EMs without pain group.In EMs pain group,with the increase of the paindegree,the serum COX-2levels rose;moderate and severe group of serum COX-2levelwere significantly higher than the mild group; At the same time moderate group also gota statistically significant with severe group.2.The genotype distribution of the COX-2gene in EMs group and control group were in line with Hardy-Weinberg equilibrium,indicating that the choice of the people in the study on genetics were random, and it hadthe group representative.3. COX-2-1195presented three genotypes of GG, GA andAA.In EMs group,the frequency of AA genotype and A allele frequency type weresignificantly higher than control group,it also presented difference between the EMswith pain and EMs without pain groups.There was significantly difference betweenthe EMs with pain and control group of GG genotype and G allele frequency.It wasrevealed a2.86-fold(95%CI=1.25~7.44) excess risk of developing EMs in theindividual for-1195AA containing haplotype compared with control and a2.33-fold(95%CI=1.09~5.62) excess risk of pain in patients of EMs with COX-2-1195AAcontaining haplotype.4. The frequencies of genotypes of COX-2-765exerted nosignificant difference between both groups.5. The relationship between COX-2genotype distribution and serum COX-2levels:genotype of-1195AA, GA, GG in EMspain group exerted statistical significance between both groups,but no significantdifference between both groups in EMs without pain group. Genotype of-1195AA inEMs pain group were higher than EMs without pain and control group,while two othergenestype presented no difference between both groups.The serum COX-2level ofvarious genes type of-765were no difference between both groups,nor between bothgenotypes.Conclusion:1.The serum COX-2level has significantly relationship with III,IVperiod of EMs with pain.The higher serum COX-2content is, the heavier pain the EMsgets.2.The polymorphism of COX-2-1195may have relevant connection with thesusceptibility of III, IV of EMs, carrying A alleles increase the risk of thepathogenesis of EMs and pain;the higher frequency of A alleles occurs, the moreserious the EMs pain is;The single nucleotide polymorphism of COX-2-1195,may playan important role in susceptibility to developing EMs and be related to pain in EMpatients.3.COX-2-1195G> A polymorphism may affect serum COX-2, and theincrease of content of AA alleles may cause the rise of serum COX-2level.4.COX-2-765G>C polymorphism have no affection with III, IV of the susceptibility of EMs, also has nothing to do with the serious of pain.