The Correlation Research Between PNPLA3Gene Polymorphism And Degree Of Liver Fibrosis And Anti-HCV Therapeutic Effect Of HCV Infected Patients

Background and aims: Hepatitis C is an infectious disease distributing all overthe world. About170million people in the world were infected by HCV,and ourcountry is a high incidence area of this disease, So the burden of this disease is quiteheavy.70%-80%of HCV infected patients could not clear spontaneously,while showinfection in continuous state. If they could not receive reasonable and effectivetreatment,30%of continuous infected patients will develop into liver cirrhosis andliver cancer finally. Interferon plus ribavirin treatment is the standard solution of antiHCV treatment,but the efficacy and disease outcome of which will be affected bymultiple factors,such as environment,virus and host. To one of the host geneticfactors in the occurrence of chronic hepatitis C development plays an important role.In recent years,the role of PNPLA3gene polymorphisms in liver diseases (NAFLD、ALD、HCV infected patients、HCC) caused widely enthusiastic research abroad,andachieved many results, but the domestic relevant research is few.PNPLA3is a kind of secretory proteins belonging to patatin phospholipasefamily, which has a specific fatty acyl hydrolase activity. Current research suggeststhat PNPLA3rs738409polymorphism is associated with HCV infection fatty changeand its severity, to the progress of liver fibrosis and cirrhosis of the liver. But theaffection of the PNPLA3polymorphism for the efficacy of anti HCV treatment hasnot unified conclusion. The purpose of the study is to explore the PNPLA3rs738409and rs139047genotype distribution in the study population, to explore the relationshipwith liver fibrosis degree of HCV infected patients, to explore the affection ofPNPLA3polymorphism for the efficiency of anti HCV treatment.Methods: Select211cases of healthy controls,538cases of chronic HCVinfected patients and138cases of spontaneous clearances to carry throughquestionnaire survey, test serum biochemical parameters and viral parameters. Select356cases of chronic HCV infected patients who are suitable for treatment to involve in the interferon plus ribavirin treatment program,and then to receive regularfollow-up test. Extract DNA from all the research object and then sent them toBomiao biological technological (Beijing) limited company to detect PNPLA3rs738409and rs139047gene site through Sequenon platform.Results:(1) rs139047conforms to genetic equilibrium, while rs738409isdisequilibrium(p=0.013).(2) The result of linkage balance test between rs738409andrs139047is as follow: D’=0.149, r2=0.015.(3) rs738409G allele and rs139047Aallele frequency were62.1%and41.9%respectively in the healthy people,65.3%and44.6%respectively in chronic HCV infected patients.(4) There were statisticdifference about rs738409genotype between chronic HCV patients and healthycontrol by logistic regression analysis (p=0.041).(5) For chronic HCV infectedpatients, there were no statistic difference about rs738409and rs139047genotypedistribution between high and low HCV load, and between different ALT or ASTlevels, also between different FibroScan stages.(6) There was no significantdifference about rs738409genotype between different liver hardness grades.(7) ForHCV patients of overall genotype, statistic significance of RVR existed betweenrs738409GG type and GC/CC type (p=0.035), and that of the SVR also existedbetween rs738409GG/GC type and CC type (p=0.016). Only for HCV patients of1btype, significance of RVR existed between rs738409GG type and GC/CC type(p=0.014), but not for2a type HCV patients.(8) For the rs139047gene, significanceof RVR also existed between AA/GA type and GG type (p=0.014). Only for the HCVpatients of1b type, significance of SVR existed between rs139047AA type andGA/GG type.Conclusion：(1) PNPLA3rs738409GG type mutation correlated with thesusceptivity and chronicity of HCV infection.(2) rs738409gene polymorphismcorrelated with RVR and SVR. GG type mutations leaded to RVR decline,GG/GCtype mutation leaded to SVR decline. What’s more, this kind of correlation isconnected with HCV genotype, GG type mutation declined RVR of HCV-1b patiients.(3) rs139047AA/GA type mutation raised RVR in all HCV genotype patients. And,AA type mutation declined SVR of HCV-1b genotype patients.