Genome-wide Association Study And Clinical Analysis Of Patients With Drug Induced Liver Injury In Fujian

Part one: Analysis of clinical characteristics,prognosis and risk factors of 308 patients with drug-induced liver injuryObjective :To analyze the clinicalcharacteristics,risk factors and prognosis of drug-induced liver injury(DILI).Methods: A retrospective analysis was conducted in 308 patients with DILI in our hospital from January 2014 to December 2016.The drugs which led to liver injury,clinical symptoms,laboratory findings,risk factors and prognosis were analyzed.Results: The mean age of the 308 patients,including 196 males(63.64%)and 112 females(36.36%),was 46.49±18.79.Antituberculosis agents were the most common agents(27.92%)inducing DILI,followed by antibiotics(21.10%)and traditional Chinese medicine(17.21%).The clinical symptoms of DILI were non-specific,including anorexia(47.73%),fatigue(42.53%),nausea(23.70%)andvomiting(21.10%).The main clinical classifications were hepatocyte-injury type(52.60%),followed by mixed type(27.60%)and cholestasis type(19.80%).After treatment,81 paitients(26.30%)recovered,213 patients relieved(69.16%),8 patients(2.60%)deteriorated,5 patients(1.62%)developed liver failure and1 patient(0.33%)died.The level of direct-responding bilirubin was an independent risk factor for the prognosis of DILI,while levels of albumin,hemoglobin and platelet were protective factors for the progess of DILI.Conclusion: Direct-responding bilirubin was an independent risk factor for the prognosis of DILI,while albumin,hemoglobin and platelet were protective factors for the progess of DILI,and they can be used as predictive factors for prognosis.Part two: Genome-wide association study of patients with drug induced liver injury in FujianObjective: To screen susceptible gene loci that might be associated with DILI of Fujian in the whole genome range.Methods: The DNA samples of 44 patients diagnosed with DILI at our hospital and 74 healthy controlswere assayed by Illumina SNP chip from January 2017 to December 2017.First,the Plink software was used to analyze the difference of all SNPs of ABCC2 between DILI and control groups.Second,genome-wide association study(GWAS)was used to screen the susceptibility genes and genetic markers,SNP sites with significant differences between the two groups were screened for GO enrichment and KEGG enrichment.Results: No significant difference of ABCC2 SNP sites was observed between DILI and control groups(P > 0.05).Numerous genes expressed differently in drug-induced liver injury.Enrichment analysis showed that these genes were mainly located at cell membrane,and mainly involved in the processes of cell adhesion,axon guidance,cell signal transduction and ion transmembrane transport.The molecular function was mainly manifested in ion channel binding,guanine nucleotide exchange factor activity,protein binding and GTP enzyme activity.These were mainly involved in glutamatergic synapse,inflammatory mediator regulation of TRP channels and MAPK signaling pathway.Conclusions: No significant correlation was found between the polymorphism of ABCC2 and the susceptibility to DILI.Multiple genes are differential expressed in DILI.Multiple genes on the membrane involved in glutamatergic synapse,TRP channels for inflammatory mediator regulation and MAPK signaling pathway may be associated with the development of DILI.