Superoxide Dismutase 2 Val16Ala Polymorphism is Associated with Amiodarone-Associated Liver Injury

Abstract

Association of SOD2 V16A single-nucleotide polymorphism (rs4880) with drug hepatotoxicity were reported but relationships with amiodarone prescriptions remained unexplored. Research was an exploratory, controlled prospective clinical trial. Patients hospitalized and treated in Clinical Center in Kragujevac, Serbia (in year 2017) were divided into experimental (using amiodarone, having liver injury, n=29, 19 males, the mean age 66.8±10.4 years), control A (neither amiodarone use nor hepatotoxicity, n=29, 19, 66.1±10.3) and control B group (using amiodarone, not having hepatotoxicity, n=29, 19, 66.8±9.8). From blood samples, among other routine biochemistry, genotyping for SOD2 polymorphism Val16Ala was conducted using real-time PCR method with TaqMan® Genotyping Master Mix and TaqMan® DME Genotyping Assay for rs4880. Patients taking amiodarone and having liver injury were mostly carriers of Val/Val (TT) genotype (13 of 24 patients, 54.2%) while Val/Ala (TC) and Ala/Ala (CC) genotypes prevailed in control group A (19 of 40, 47.5%) and control group B (9 of 23, 39.1%), respectively (2=10.409, p=0.034). Frequency of Val (T) and Ala (C) alleles were 0.51 and 0.49, respectively in the whole study sample (Hardy Weinberg equilibrium, 2=0.56, p=0.454). Carriers of TT genotype had significantly higher ALT (437.0±1158.0 vs 81.9131.5 U/L), total bilirubin (28.320.5 vs 15.313.0 mol/L) and total bile acid concentrations (10.910.2 vs 6.45.3 mol/L) compared to carriers of TC genotype (U=2.331, p=0.020, U=3.204, p=0.001 and U=2.172, p=0.030, respectively). Higher incidence of 47T allele of SOD2 was inpatients with amiodarone-associated liver injury as compared to patients on amiodarone not experiencing hepatotoxic effects.

Impact of Superoxide Dismutase Genetic Polymorphism (Sod2 Val16ala) and Superoxide Dismutase Level on Disease Severity in a Cohort of Egyptian Sickle Cell Disease Patients in Egypt

“…It has been reported that human peripheral blood mononuclear cells from the carriers of TT genotype of SOD2 produced more proinflammatory cytokines such as IL-1, IL-6, TNF-α and IFN-γ than those having the CC genotypes, which could affect the hepatocyte’s function. 23 The pathology of chronic hemolytic status among SCD patients is a major contributing factor to gall stone formation.…”