| Objectives:It is the main factor for patients who die from either liver failure orhepatocellular carcinoma that they chronically infect hepatitis B virus (HBV). It’snecessary to do more researches about HBV-related chronic liver diseases. Aldehydedehydrogenase2(ALDH2), as the most common enzyme defect in human, affects8%of the population in the world. We observe that there is a good geographicalcorrelation between the prevalence of the mutant ALDH2*2alleles and HBVinfection. Populations that demonstrate a high ALDH2*2prevalence are all locatedin HBV-endemic areas. The relationship of ALDH2*2alleles and the progress ofHBV-related liver diseases is still unknown. In our study, we detect thepolymorphisms of ALDH2(rs671, rs10849970and rs886205) to explore theassociation of ALDH2gene polymorphisms with HBV-related chronic hepatitis,liver cirrhosis and hepatocelluar carcinoma in population of Jilin Province.Methods:We selecte283healthy individuals in Jilin area as normal control group (groupNC), the patients with HBV associated chronic liver diseases are647cases,including102cases with HBV-related chronic hepatitis group (CHB group),264cases with HBV-related cirrhosis group (LC group),281cases with HBV-relatedliver cancer group (HCC group). Genomic DNA is extracted from blood samples,and ALDH2genotypes are detected by MALDI-TOF-MS technology. We applyanalysis software SPSS17.0to analyze the date. MALDI-TOF-MS is used to analyze polymorphisms of ALDH2gene, then calculate the frequencies of genotypesand alleles. The SNPs are tested for Hardy-Weinberg eauilibrium by χ2test. TheSNPs are conducted by χ2test to estimate odds ratio (OR) and95%confidenceinterval (95%CI) and analyze the association of ALDH2gene polymorphisms withHBV-related chronic hepatitis, liver cirrhosis and HCC susceptibility. Haplotyeanalysis is conducted by Unphased sofeware. Multi-factor unconditioned logisticregression is used to estimate whether drinking, smoking and gene interactionbetween the two groups affect the genetic susceptibility to disease or not.Results:1.The differences of age and gender composition between NC group and CHB,LC, HCC group are not statistically significant (P>0.05). In both control group andeach case group, genotypes of ALDH2rs10849970and rs886205are inHardy-Weinberg eauilibrium (P>0.05). In NC group, CHB and LC group genotypesof ALDH2rs671are in Hardy-Weinberg eauilibrium (P>0.05) while in HCC groupgenotypes of ALDH2rs671are not in Hardy-Weinberg eauilibrium (P<0.05).2. There are GG, GA and AA genotypes in ALDH2rs10849970. Tested by χ2thedifferences of the genotype and allele frequencies between NC group and CHB, LC,HCC group are not significant (P>0.05).Those results indicate the polymorphism ofrs10849970is not associated with HBV-related liver diseases.3.There are CC, CT and TT genotypes in ALDH2rs886205.Tested by χ2thedifferences of the genotype and allele frequencies between NC group and CHB, LC,HCC group are not significant (P>0.05).Those results indicate the polymorphism ofrs886205is not associated with HBV-related liver diseases.4. There are GG, GA and AA genotypes in ALDH2rs671. Tested by χ2thedifferences of the genotype frequencies between NC group and CHB, LC, HCC group were significant (P<0.05).The GG genotype frequencies and the dominantmodel GA+AA genotype frequencies between the control group and CHB, LC,HCC group are significant (P<0.05).Those results indicate the polymorphism ofrs671may be associated with HBV-related liver disease.5. There are GG, GA and AA genotypes in ALDH2rs671. Comparing with GGgenotype, we find AA genotype is associated with susceptibility to LC (P<0.05) andit may be a risk factor for LC. Comparing with GG genotype, we find GA genotypeis associated with susceptibility to HCC (P<0.05) and it may be a risk factor forHCC.The dominant model GA+AA is associated with susceptibility to HCC (P<0.05)and it may be a risk factor for HCC.Comparing with G allele we find A allele isassociated with susceptibility to HCC (P<0.05) and it may be a risk factor forHCC.Those results indicate the polymorphism of rs671may be associated withHBV-related liver cirrhosis and HBV-related HCC.6. Comparing with GG genotype,there is significant difference in thedistribution of GA genotype between LC and HCC groups(P<0.05). We find thedominant model GA+AA is also associated with HCC risk compared with LC.Thoseresults indicate the polymorphism of rs671is associated with HCC.7. We conduct haplotype analysis for ALDH2rs671, rs10849970and rs886205.The risk of the G-A haplotype carriers suffering from HCC decrease to0.665comparing with A-A haplotype carriers,indicating A-A haplotype may be a riskfactor for HCC.8. We also investigate gene–environment interactions on the progress ofHBV-related liver diseases.We then test whether the ALDH2rs671interact withalcohol consumption and smoking status in the progress of HBV-related liverdiseases.No interaction between rs671and alcohol consumption on HBV-related liver diseases is observed (all P>0.05).No interaction between rs671and smokingstatus on HBV-related liver disease was observed (all P>0.05).Conclusion:1. The ALDH2rs10849970and rs886205polymorphisms may do nothing withsusceptibility to HBV-relative liver diseases in Jilin province. The dominant modelGA+AA of ALDH2rs671is associated with susceptibility to HBV-relative liverdiseases.2. AA genotype of ALDH2rs671is associated with LC susceptibility, and itmay be a risk factor for LC. GA genotype and the dominant model GA+AA areassociated with HCC susceptibility, and it may be a risk factor for HCC. A allele isassociated with HCC susceptibility, and it may be a risk factor for HCC.3. GA genotype and the dominant model GA+AA of ALDH2rs671areassociated with the outcome of HBV-related liver diseases, which may be a riskfactor for HCC.4. The risk of the AA haplotype conducted from ALDH2rs671and rs10849970are associated with the outcome of HBV-related liver diseases, which might be a riskfactor for HCC.5. We also investigate gene–environment interactions on the progress ofHBV-related liver diseases.We then test whether the ALDH2rs671interacted withalcohol consumption and smoking status in the progress of HBV-related liverdiseases.No interaction between rs671and alcohol consumption on HBV-relatedliver diseases is observed (all P>0.05).No interaction between rs671and smokingstatus on HBV-related liver disease is observed (all P>0.05). |
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