RT Journal Article
T1 Genome-Wide Association Study of Metamizole-Induced Agranulocytosis in European Populations.
A1 Cismaru, Anca Liliana
A1 Rudin, Deborah
A1 Ibañez, Luisa
A1 Liakoni, Evangelia
A1 Bonadies, Nicolas
A1 Kreutz, Reinhold
A1 Carvajal, Alfonso
A1 Lucena, Maria Isabel
A1 Martin, Javier
A1 Sancho Ponce, Esther
A1 Molokhia, Mariam
A1 Eriksson, Niclas
A1 Krähenbühl, Stephan
A1 Largiadèr, Carlo R
A1 Haschke, Manuel
A1 Hallberg, Pär
A1 Wadelius, Mia
A1 Amstutz, Ursula
K1 dipyrone
K1 drug-induced agranulocytosis
K1 genome-wide association study
K1 metamizole
K1 pharmacogenetics
AB Agranulocytosis is a rare yet severe idiosyncratic adverse drug reaction to metamizole, an analgesic widely used in countries such as Switzerland and Germany. Notably, an underlying mechanism has not yet been fully elucidated and no predictive factors are known to identify at-risk patients. With the aim to identify genetic susceptibility variants to metamizole-induced agranulocytosis (MIA) and neutropenia (MIN), we conducted a retrospective multi-center collaboration including cases and controls from three European populations. Association analyses were performed using genome-wide genotyping data from a Swiss cohort (45 cases, 191 controls) followed by replication in two independent European cohorts (41 cases, 273 controls) and a joint discovery meta-analysis. No genome-wide significant associations (p < 1 × 10-7) were observed in the Swiss cohort or in the joint meta-analysis, and no candidate genes suggesting an immune-mediated mechanism were identified. In the joint meta-analysis of MIA cases across all cohorts, two candidate loci on chromosome 9 were identified, rs55898176 (OR = 4.01, 95%CI: 2.41-6.68, p = 1.01 × 10-7) and rs4427239 (OR = 5.47, 95%CI: 2.81-10.65, p = 5.75 × 10-7), of which the latter is located in the SVEP1 gene previously implicated in hematopoiesis. This first genome-wide association study for MIA identified suggestive associations with biological plausibility that may be used as a stepping-stone for post-GWAS analyses to gain further insight into the mechanism underlying MIA.
PB MDPI AG
YR 2020
FD 2020-10-29
LK http://hdl.handle.net/10668/16529
UL http://hdl.handle.net/10668/16529
LA en
NO Cismaru AL, Rudin D, Ibañez L, Liakoni E, Bonadies N, Kreutz R, et al. Genome-Wide Association Study of Metamizole-Induced Agranulocytosis in European Populations. Genes (Basel). 2020 Oct 29;11(11):1275.
DS RISalud
RD Oct 25, 2025