| Objectives: Infection of Hepatitis B virus(HBV) is still the main cause of Pathogenic factor in China that induce end-stage chronic liver disease, cirrhosis, liver failure and even hepatocellular carcinoma and finally result in death. There is many uncertain fields to be explored during the HBV-related liver disease progress. Interleukin- 22(IL-22) is a newly discovered cytokines that secreted mainly by lymphocytes. Many studies have indentified that IL-22 play an protective role of anti-inflammatory, anti-oxidative stress, promoting regeneration and tissue repair in many organs including liver.meanwhile, there are also researches reported that IL-22 may acts as a pathological factor in some certain pathophysiological state such as chronic inflammation and cancer, the mechanism of the effects of IL-22 remains unknow so far. In this experiment we tested the gene polymorphisms of IL-22 rs1026788, rs2227472, rs2227491, rs2227485, rs1179249, rs2046068,rs2227473 and rs7314777,analysed the potential relationship between gene polymorphisms and HBV-related hepatitis, cirrhosis, and hepatocellular circinoma among population in Jilin Province, Northeast China.Methods: We celected 649 HBV-related liver disease patients in case groups, including 103 cases with chronic hepatitis B(CHB group), 264 cases with liver cirrhosis(LC group) and 282 cases with hepatocellular carcinoma(HCC group). Genomic DNA samples were extracted from whole solidification blood and the MALDI-TOF-MS technology was employed to detect genotypes. Analysis software SPSS 17.0 to were applied to analyze the date. MALDI-TOF-MS was used to analyze polymorphisms of IL-22 gene.Then calculated the frequencies of genotype and allele.The SNPs were tested for Hardy-Weinberg eauilibrium by χ2 test. The SNPs were conducted by χ2 test to estimate odds ratio(OR) and 95% confidence interval(95%CI),analyzing the association of IL-22 polymorphisms and HBV-related hepatitis, liver cirrhosis and HCC susceptibility. Haplotye analysis was conducted by Unphased sofeware. Using multi-factor unconditioned logistic regression to estimate whether gene,smoking, and drinking interaction between the two groups and affect the genetic susceptibility to disease or not.Results: 1.The age and gender distribution differences between CHB,LC and HCC groups were not statistically significant(P>0.05). In CHB group, LCgroup and HCCgroup, All of the IL-22 rs1026788, rs1179249, rs2046068, rs2227472, rs2227473, rs2227485, rs2227491 genotypes were in Hardy-Weinberg eauilibrium(P>0.05); rs7314777 was not in Hardy-Weinberg eauilibrium(P<0.05), but it also fits for our study because cases with HBV related liver diseases and not health group were control group in our study. 2.There were TT,CT and CC genotypes in IL-22 rs1026788,rs2227472, rs22274723,rs7314777 and rs2227491;CC,AC and AA genotypes in IL-22 rs2046068, GG,AG,AA genotypes in IL-22 rs2227485,GG,GT,TT genotypes in IL-22 rs1179249.Tested by χ2 the the genotype and allele frequencies distribution differences between CHBgroup,LC group and HCC group were not significant(P>0.05). There were G/T allele in IL-22 rs1179249,Tested by χ2 the the allele frequencies distribution differences between CHB group and LC group and HCC group were significant(P=0.044);There were T/C allele in IL-22 rs 2227472,Tested by χ2 the the allele frequencies distribution differences between CHB group and LC group and HCC group were significant(P=0.049).No significant IL-22 alleles distribution diferences in rs1026788, rs2046068, rs2227473, rs2227485, rs2227491 and rs7314777 were found among CHB group,LCgroup and HCC group in in IL-22(all P>0.05). These results suggested that single IL-22 rs1179249,rs2227472, rs1026788,rs2046068,rs2227473,rs2227485,rs2227491 and rs7314777 genotypes might have no significant association with HBV-related liver disease. 3.Comparison between CHB group and LC group,114 haplotypes polymorphism frequencies distributed between the two groups were signgficant(P<0.05),among which 21 haplotypes polymorphsm P values were in 0.006-0.009,86 in 0.01-0.019 and 6 in 0.02-0.048. Comparison between LC group and HCC group,95 IL-22 haplotypes polymorphsm were significant between the two groups(P<0.05),among which 18 P values are in 0.024-0.03,43 in 0.031-0.04 and 34 in 0.041-0.05. Comparison between CHB group and HCC group,no signgficant difference of haplotype gene polymorphysm was observed(all P>0.05). Polymorphism of rs2227491&rs2227473 and were significantly associated with CHB to LC;rs2046068&rs2227491&rs2227473&rs7314777 were associated with LC to HCC. 4.Individual with A-A is more susceptible to LC than with A-G. 5.We divided our objectives into two groups according smoking and alcohol consumption status and analysed the genotypes frenquencies distribution of each group between CHB vs LC,LC vs HCC and CHB vs HCC.Analysed by χ2 test we found rs2227485,rs2227491 genotypes in alcohol group were significant between LC vs HCC(P<0.05);rs1179249 genotypes in no smoking group were significant between LC vs CHB(P<0.05); rs1026788,rs2227485,rs2227491 genotypes in no smoking group were significant between LC vs HCC(P<0.05);rs1179249 genotypes in no alcohol group were significant between LC vs CHB(P<0.05). 6.We also investigated gene–environment interaction on the progress of HBV-related liver disease.No interaction between IL-22 SNPs and alcohol consumption on HBV-related liver disease was observed(all P > 0.05).No interaction between IL-22 SNPs and smoking status on HBV-related liver disease was observed(all P > 0.05).Conclusion: 1.IL-22 single polymorphism might not be associated with progression of HBV-related liver disease among Population in Jilin Province,Northeast China. 2.IL-22 genotype polymorphisms may be related to progression of HBV-related liver diseases.And the correlation was more significant in CHB to LC than LC to HCC among population in Jilin Province, Northeast China. 3.IL-22 rs2227491&rs2227473 gene polymorphism might play a significantly important role in progression of HBV-related liver disease. 4.Individual carry A-A genotype might be a risk factor for HBV-related liver cirrhosis. 5.We also investigated gene–environment interaction on the progress of HBV-related liver disease.No interaction between IL-22 SNPs and alcohol consumption on HBV-related liver disease was observed(all P > 0.05).No interaction between IL-22 SNPs and smoking status on HBV-related liver disease was observed(all P > 0.05). |
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