Novel Biomarker for Liver Injury Risk Is Identified
Alterations in immune regulation are believed to contribute to idiosyncratic drug-induced liver injury, according to the researchers of a new study. The determination comes after the identification of rs2476601 in PTPN22 as a non-human leukocyte antigen variant—a variant that has been associated with increased risk of autoimmune diseases.
To reach this conclusion, the researchers performed a genome-wide association study on 2048 participants with idiosyncratic drug-induced liver injury and 12,429 participants without the disease who acted as controls. The participants were of European, African American, and Hispanic backgrounds.
To validate their study’s findings, the researchers then analyzed the DNA of 113 additional participants with idiosyncratic drug-induced liver injury and 239,304 additional controls.
The study and its validation both showed an association of idiosyncratic drug-induced liver injury with rs2476601.
With an allele frequency of 13.3%, the strongest association was observed for amoxicillin- and clavulanate-associated idiosyncratic drug-induced liver injury in persons of European ancestry. In fact, rs2476601 doubled the risk for drug-induced liver injury among those with the HLA risk alleles A*02:01 and DRB1*15:01 in that population.
Among all ethnic groups, minor allele frequency showed the same effect size.
Polymorphism was associated with drug-induced liver injury of other causes, with an allele frequency of 11.5%.
—Colleen Murphy
Reference:
Cirulli ET, Nicoletti P, Abramson K, et al. A missense variant in PTPN22 is a risk factor for drug-induced liver injury [published online January 18, 2019]. Gastroenterology.