| Background and objective:Crohn disease(CD) is an chronic idiopathic inflammatory disorders of the gastrointestinal tract. Although the exact etiology of CD remains unknown, it is now generally accepted that the pathogenesis of CD is complex and may involve environmental, genetic, infectious and immunological factors. Recent research indicated that inappropriate intestinal immune responses which activated by overproduction of several inflammatory cytokines, might play a key role in the CD occurrence.Interleukin-27(IL-27) is a novel heterodimeric cytokine regarded as a member of IL-6/IL-12family, which secreted mainly by stimulated antigen-presenting cells such as macrophages and dendritic cells, and composed of two subunits:the Epstein-Barr virus-induced gene3(EBi3) and IL-27p28. Same to IL-12in the structure and function, IL-27take part in the pathogenesis of several chronic disorders such as immunity related diseases, infectious diseases and neoplasms. Nowadays, three polymorphisms including964T>C in the promoter region,2905T> G in the exon2and4730T> C in the exon4are widely studied in IL-27p28with various diseases. In2009, Li et al. reported that the IL-27rs153109polymorphism was significantly associated with the susceptibility of CD in the Korean population. However, the role of IL-27 polymorphisms in the Chinese CD patients susceptibility was unknown. Therefore, in our study, we conducted an association study to analysis the polymorphisms of IL-27gene with CD occurrence in Zhejiang Province in China.Subjects and methods:1.Subjects:We enrolled75(40patients from The First Affiliated Hospital of ZheJiang Uiversity School Of Medicine and35from Shangyu People’s Hospital) sporadic patients with CD and80healthy volunteers from Jan2007to Dec2011in this study. In75CD patients, there are41males and34females with average37.43±12.45years (ranged from8to67years). The mean duration of the disease was5.37±4.29years. The mean CDAI was183.47±53.61. We also selected80healthy controls including45males and35females with age ranged from18-60years (average36.21±11.54). All patients had a well-established diagnosis of CD according to Chinese IBD standard clinical criteria. Patiets with following diseases were exclued:1. non-Chinese Han population;2.with other immunity-related disease; with other serious disorders in cardiac,lung, liver,kidney, nerve or mental sickness;4. with DM or other endocrine diseases;5. recently with evident infectious history;6.pregnant patient;7. Trauma patients. Cases and controls were well matched by age and gender.2.Methods:The g.-964T> C, g.2905T> G and g.4730T> C polymorphisms of IL-27p28gene were analysed by polymerase chain reaction-ligase detection reaction (PCR-LDR). 3.Statistical analysisComparisons between CD patients and controls were conducted by unpaired t-test for continuous variables and by x2test for categorical variables. To avoid gross genotyping error, all polymorphisms were checked for consistency with Hardy-Weinberg equilibrium on a contingency table of observed-versus-predicted genotype frequencies by using Pearson x2test or Fisher’s exact test using SHEsis software. Genotypes were compared by Logistic regression analysis and odds ratio (ORs) and95%confidence interval (CI) were estimated with SPSS16.0. Statistical significance was defined as P<0.05.Results and discussion:There were no deviations from Hardy-Weinberg equilibrium for all studied polymorphisms in controls or cases (P>0.05). However, the genotype and allele frequencies at g.-964T> C site in cases group showed significant difference (P<0.05, OR=1.94,95%CI=1.22-3.10), while those at g.2905and g.4730sites showed no significant difference with those in control group(P>0.05). Therefore, the IL-27p28-964T> C polymorphism gene might be related to the susceptibility to Crohn’s disease in Zhejiang area Han population. However, no relationship was observed between the IL-27p282905T>G or4730T> C polymorphism and Crohn’s disease in the same population.Interleukin-27(IL-27) is a novel heterodimeric cytokine composed of two subunits: the EBi3and IL-27p28. Through the IL-27receptor, IL-27activates JAK/STAT signaling pathway to induce cytokine and chemokine production, and play a dual pro-inflammatory and anti-inflammatory role in the immunity regulation.On one hand, IL-27not only activates STATland STAT3signaling pathways in naive CD4+T cells and enhances proliferation in naive CD4+T cells, promotes inflammation by inducing naive T cells to differentiate into the Thl subset, but also synergizes with IL-12in primary IFN-γ production; one the other hand, promotes Th1cells to differentiate via ICAM-1/LFA-1pathways. Villarino et al. revealed that IL-27R deficiency delays the onset of colitis and protects from helminth-induced pathology in a model of chronic IBD. Therefore, IL-27played an important role in the immunity regulation in CD occurrence and development, and regarded as a logical candidate susceptible gene for CD.In this study, there were no deviations from Hardy-Weinberg equilibrium for all studied polymorphisms in controls, so the samples in this study were representative for population in Zhejiang Province. Moreover, the genotype and allele frequencies at g.964T> C site in trial group showed significant difference (P<0.05), indicating the-964T> C polymorphism gene might be related to the susceptibility to CD in Zhejiang area Han population, which was in accord with previous study conducted by Li et al. in the Korean population. Whereas those at g.2905and g.4730sites showed no significant difference with those in control group, suggesting that there was no relationship between the IL-272905T> G or4730T> C polymorphism and CD in the same population. Given several uncertain factors such as racial differences, insufficient number of samples, we could not exclude the association between these two polymorphisms with CD in other different populations and there might be still other unidentified polymorphisms which influenced the development of CD.Considering several limitations in this study, further association studies utilizing a large sample size from multi-centers should be initiated to verify this association, and so as to screen and find out susceptible gene for CD in Chinese Han population and provide supporting evidence for further genetic diagnosis and treatment in CD.Conclusions: 1.The genotype and allele frequencies at g.-964T> C site in trial group showed significant difference, indicating the-964T> C polymorphism gene might be related to the susceptibility to CD in Zhejiang area Han population.2.The genotype and allele frequencies at g.2905and g.4730sites showed no significant difference with those in control group, suggesting that there was no relationship between the IL-272905T>G or4730T>C polymorphism and CD in Zhejiang area Han population. |
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