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The Association between Gene Promoter Region Polymorphisms of Interleukin-18Gene and the Susceptivity of Endometriosis

Author: ZhangMeiLing
Tutor: CaoYunXia
School: Anhui Medical University,
Course: Obstetrics and Gynaecology
Keywords: Endometriosis IL-18 cytokine gene polymorphism
CLC: R711.71
Type: Master's thesis
Year: 2012
Downloads: 49
Quote: 0
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Background Endometriosis is a common gynecologic disease amongreproductive-aged women. Its common clinical symptoms include dysmenorrhea,noncyclic pelvic pain,dyspareunia, and infertility. Endometriosis shares somecharacteristics with cancer, such as clonality, ability to invade surrounding tissues andmaybe capacity to metastasize These bring to a serious impact on physical and mentalhealth. In recent years an increase of endometriosis incidence varies from10to15%.It is accompanied by infertility which occurs in40%of endometriosis women.Several studies have confirmed that EMs is a multi-gene genetic disease,thedevelopment of which is influenced by interactions between multiple genes andenvironmental factors. Other characteristics of EMs show a tendency to familialaggregation.Very little is known about its etiology and pathogenesis. Moreover,cytokine-mediated immune and inflammatory responses have been thought to play animportant role in the pathogenesis of endometriosis.Which may be the importantcause in the occurrence and development of EMs.IL-18encodes a pro-inflammatory cytokine located on chromosome11q22.2-22.3.It is composed of six exons and five introns.The IL-18molecule shares structuralsimilarities with the IL-1family. IL-18, originally described as IFN-r-inducing factormediates both Th1and Th2driven immune responses.IL-18is synthesized byactivated mononuclear macrophages and dendritic cells and is able to augment theT-helper1responses and cytotoxic activity of natural killer cells.Several researchesshowed that the elevation of IL-18in the peritoneal fluid of endometriosis patients hassuggested its role in the pathogenesis of this disease. So IL-18is a promisingcandidate gene. Considerable evidence shows that IL-18gene polymorphisms areassociated with ovarian cancer, recurrent miscarriage, polycystic ovary syndrome, cervical cancer, hepatitis et al.Several single nucleotide polymorphisms (SNPs) in thisgene have been identified. Some of these variants,-607C/A(rs1946518) and-137G/C (rs187238) in the promoter region have been confirmed to influence IL-18geneexpression.A recent study has reported the association between EMs and the IL-18–607C/A polymorphism in a Turkish population.Ayaz Ldemonstrated the associationof the IL-18607*A homozygous A allele with a higher susceptibility to EMs in aTurkish population.The distribution of IL-18functional polymorphisms could bedifferent in populations as a result of ethnic differences and environmentalinfluences.The association between EMs and the IL-18(–607C/A and-137C/G)polymorphisms has not, however, been studied in other ethnic cohorts. The aim of thepresent study was to investigate whether two SNPs in IL-18are associated withsusceptibility of Chinese Han women to EMs.Objective The purpose of this study was to evaluate whether two polymorphismsin the IL-18gene promoter at positions607C/A (rs1946518) and137G/C (rs187238)were predisposing genetic factors for EMs in a Chinese Han population.Method The study cohort included230patients diagnosed with severeendometriosis. Control group consisted of230healthy women.Genotyping of theIL-18gene polymorphisms607C/A and137G/C, was performed by polymerasechain reaction and restriction fragment length polymorphism analysis(PCR-RFLP).Result There were no significant differences in distribution of genotypes or allelesin either of the two IL-18single nucleotide polymorphisms between EMs patients andcontrols. However, subsequent analysis revealed haplotype CC is lower in patientsthan in controls (P=0.014, odds ratio [95%confidence interval]=0.293[0.104-0.825]).Conclusion This is the first report demonstrating that functional IL-18genepolymorphisms do not influence the susceptibility to severe EMs in the Chinese Hanpopulation.

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CLC: > Medicine, health > Obstetrics and Gynaecology > Gynecology > Other diseases of the female genital > Endometriosis
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