First step towards precision medicine for antithyroid drug-induced agranulocytosis

Antithyroid drugs are a cornerstone of treatment for hyperthyroidism, but can cause life-threatening agranulocytosis. In The Lancet Diabetes & Endocrinology, Pär Hallberg and colleagues 1 Hallberg P Eriksson N Ibañez L et al. for the EuDAC collaboratorsGenetic variants associated with antithyroid drug-induced agranulocytosis: a genome-wide association study in a European population. Lancet Diabetes Endocrinol. 2016; (published online May 3.)http://dx.doi.org/10.1016/S2213-8587(16)00113-3 PubMed Google Scholar present results from the EuDAC study, a genome-wide association study of drug-induced agranulocytosis in European people, focusing on cases caused by antithyroid drugs. Their results are based on 39 agranulocytosis cases caused by antithyroid drugs and 5170 population controls from four European countries (Sweden, Spain, France, and Germany). They used genome-wide single nucleotide polymorphism (SNP) genotypes and the imputed HLA genotypes for the analysis. They identified HLA-B*27:05 as the major susceptibility gene (odds ratio [OR] 7·30, 95% CI 3·81–13·96, p=1·91 × 10−9). Three SNPs (rs652888, rs19956443, and rs1071816) in the HLA region also showed association signals and were used to build a regression model for risk prediction. Genetic variants associated with antithyroid drug-induced agranulocytosis: a genome-wide association study in a European populationIn white European people, antithyroid drug-induced agranulocytosis was associated with HLA-B*27:05 and with other SNPs on chromosome 6. In the future, carriers of these variants could be placed under intensified monitoring or offered alternative treatment for hyperthyroidism. Full-Text PDF