Molecular Epidemiological Study On The Association Of RIG-?-like Receptor Gene Polymorphism With Chronicity And Prognosis Of HCV Infection

Section 1 Association between RIG-?-like receptor gene polymorphisms and chronic HCV infectionHepatitis C virus(HCV)infection is a global social problem that seriously jeopardizes public health.HCV can cause acute or chronic infections.Acute infections usually have no obvious symptoms.About 15%-45% of infected people can eliminate the virus within 6 months of infection without any treatment.The remaining 60%-80% of infected people Will develop into a chronic infection.After the HCV invades the body,the innate immune system is the first line of defense for identifying viruses.The RIG-? like receptors(RLRs)in the pathogen model molecular recognition receptor can mediate innate immune response by recognizing the HCV virus.The genetic variation of its genes can affect the body's ability to clear HCV through the host's innate immune response,and ultimately lead to different infection outcomes.Therefore,studying the relationship between RIG-?-like receptor gene polymorphism and chronic HCV infection can provide a basis for prevention and control of HCV infection outcome.[Objectives] To investigate the relationship between RIG-?,MDA5 and LGP2 gene polymorphisms and chronic HCV infection,and provide a scientific basis for controlling the replication and spread of HCV.[Methods] A case-control study design was used to collect XX patients with HCV at high risk for follow-up data,including 596 patients in the self-limited group and 996 patients in the continuous infection group.15 single nucleotide polymorphisms(SNPs)(RIG-? rs12236816,rs3824456,rs10813831,rs10738889,rs9695310,rs3205166,rs11795343,rs17217280,rs659527;MDA5 rs3747517,rs2111485,rs1990760,rs10930046;LGP2 rs2074158,rs2074160)by Taqman-MGB probe technology were genotyped to analyze the effect of the above genetic polymorphism on the chronicity of HCV infection,and establish a scientific genetic model of RIG-?-like receptor pathway.[Results] RIG-? rs659527,MDA5 rs2111485,MDA5 rs1990760 and LGP2 rs2074158 were associated with persistent infection(P < 0.0033).Carry RIG-? rs659527-G allele(dominant model: adjusted OR = 1.40,95% CI = 1.12-1.75,P = 0.003),MDA5 rs2111485-G allele(dominant model: adjusted OR = 1.46,95% CI = 1.15-1.84,P = 0.002),MDA5 rs1990760-T allele(dominant model: adjusted OR = 1.57,95% CI = 1.26-1.96,P < 0.001)and LGP2 rs2074158-G allele HCV-infected individuals(additive model: adjusted OR = 1.46,95% CI = 1.24-1.73,P < 0.001)were more likely to develop persistent infection status.Stepwise regression analysis showed that RIG-? rs659527,MDA5 rs1990760,MDA5 rs2111485,age,ALT and AST were independent influencing factors of HCV persistent infection.The combined effect analysis of RIG-? rs659527-G,MDA5 rs1990760-T and MDA5 rs2111485-G unfavorable alleles showed that with the increase of unfavorable alleles,the risk effect of joint action increased,carrying 4-6 Unfavorable alleles are more likely to be persistently infected(carrying 2-3 unfavorable alleles: OR = 1.47,95% CI = 1.03-2.09;carrying 4-6 adverse alleles: OR = 2.25,95 %CI = 1.51-3.34).The mutation of RIG-? rs659527 was related to the expression of RIG-? gene in whole blood(P = 0.037).[Conclusion] RIG-? rs659527,MDA5 rs2111485,MDA5 rs1990760 and LGP2 rs2074158 alleles are risk factors for self-limiting clearance of HCV-infected patients,RIG-? rs659527,MDA5 rs1990760,MDA5 rs2111485,age,ALT and AST It is an independent influencing factor for persistent HCV infection.RIG-? rs659527 has potential biological functionsSection 2 Association between RIG-?-like receptor gene polymorphisms and treatment response in patients with chronic hepatitis CThe immune response of some people infected with HCV can clear the virus,so hepatitis C does not always need treatment,but in those with chronic hepatitis C virus infection,the risk of cirrhosis within 20 years is 15%-30%.The most common treatment in China before is pegylated interferon plus ribavirin(PEG IFN-?/RBV),which can significantly improve the sustained virological response(SVR)in patients with chronic HCV infection.The mortality caused by HCV infection is reduced,but about 40% of patients still have poor or no response.The genetic variation of the RIG-?-like receptor gene can affect the viral clearance ability of HCV patients by interfering with the host immune response.To explore the relationship between RIG-?-like receptor gene polymorphism and treatment response in patients with chronic hepatitis C,it can provide a new strategy for individualized and precise prevention and treatment of HCV.[Objectives] To explore the relationship between RIG-?,MDA5 and LGP2 gene polymorphisms in the treatment response of HCV patients,and to provide a basis for the development of individualized treatment plans and new prevention strategies.[Methods] A prospective cohort study design was used to enroll xx patients with PEG IFN-?/RBV regimen.These cases were followed up regularly at baseline,at 4,12,24,and 48 weeks of treatment and 24 weeks after the end of treatment to detect HCV RNA load,thereby judging the patient's therapeutic effect.The Taqman-MGB probe technique was used to genotype 15 SNPs on the RIG-?-like receptor family RIG-?,MDA5 and LGP2 genes to study the effect of genetic variation of the family-related genes on HCV response.[Results] RIG-? rs3205166,RIG-? rs3824456,and baseline blood glucose levels were independent factors influencing the sustained virological response of HCV.Patients with RIG-? rs3205166 mutation genotype were more likely to obtain SVR(adjusted OR = 1.09,95% CI).= 1.01-1.17,P = 0.021),and the higher the baseline fasting blood glucose level(adjusted OR = 0.76,95% CI = 0.68-0.86,P < 0.001)and the RIG-? rs3824456 mutant genotype(adjusted OR = 0.91,Patients with 95% CI = 0.84-1.00,P = 0.045)were less likely to have SVR.The area under the ROC curve consisting of these three variables is 0.7375.RIG-? rs3205166 and RIG-? rs3824456 haplotype analysis showed that it is not easy to obtain SVR with AC haplotype compared with CG haplotype(adjusted OR=0.44,95% CI: 0.22-0.90,P= 0.025).HCV patients carrying the RIG-? rs3205166 CA/CC genotype had a faster decline in viral load,whereas HCV patients carrying the RIG-? rs3824456 GC/CC genotype had a slower viral load.RIG-? rs3824456 is located at the highest peak of the h3k27 ac histone marker in seven cell lines,suggesting a potential biological function.[Conclusion] RIG-? rs3205166,RIG-? rs3824456,and baseline blood glucose levels are independent influencing factors of HCV antiviral response,and RIG-? rs3824456 has potential biological functions.