Clinical Investigation

Abstract

Failure to replicate a previously reported GWAS association between KCNJ1 gene and co-amoxiclav-induced liver injuryBackground: Co-amoxiclav is associated with Drug-Induced Liver Injury (DILI).HLA genotype is an important predictor of DILI susceptibility but it is likely that non-HLA risk factors also contribute.This study aimed to characterize non-HLA risk factors in larger cohorts than previously.Although KCNJ1 is known for its regulation of kidney activities through modulation of potassium homeostasis, the association seen between this gene and co-amoxiclav DILI, detected in a previous Genome-Wide Association Study (GWAS), which was close to p-value threshold significance, was stimulating to investigate its role in DILI susceptibility.Methods: A variant (rs2855790) in KCNJ1 was genotyped to extend the previous findings.73 coamoxiclav adjudicated DILI cases and 75 community controls were genotyped using RFLP-PCR assay.Drug causality of the cases was assessed using the RUCAM method.The data obtained were analyzed for its Odds Ratio (OR) value and Fisher's exact test was used to generate a p-value.Results: Although, variant allele frequency in cases were much lower (15.8%)than in controls (24.7%);however, the difference was not statistically significant (OR=0.58,95% CI=0.29-1.1;P=0.13).Hence, the previously reported association with KCNJ1 (rs2855790) could not be confirmed in this new cohort of co-amoxiclav DILI. Conclusion:Given the biological role of KCNJ1 in the kidney, not the liver, this gene was not a very biologically plausible candidate as a DILI gene so the final result obtained for this is not too surprising.

Part of CIRS Nexus · Curated by Lauren Lowenstein, The Biotoxin Lady