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21 pages, 1794 KiB  
Article
Genome-Wide Association Study of Metamizole-Induced Agranulocytosis in European Populations
by Anca Liliana Cismaru, Deborah Rudin, Luisa Ibañez, Evangelia Liakoni, Nicolas Bonadies, Reinhold Kreutz, Alfonso Carvajal, Maria Isabel Lucena, Javier Martin, Esther Sancho Ponce, Mariam Molokhia, Niclas Eriksson, EuDAC collaborators, Stephan Krähenbühl, Carlo R. Largiadèr, Manuel Haschke, Pär Hallberg, Mia Wadelius and Ursula Amstutz
Genes 2020, 11(11), 1275; https://doi.org/10.3390/genes11111275 - 29 Oct 2020
Cited by 10 | Viewed by 5888
Abstract
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. [...] Read more.
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. Full article
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