eprintid: 10138683 rev_number: 18 eprint_status: archive userid: 608 dir: disk0/10/13/86/83 datestamp: 2021-11-25 12:26:17 lastmod: 2021-12-02 00:22:09 status_changed: 2021-11-25 12:26:17 type: article metadata_visibility: show creators_name: Austin-Zimmerman, I creators_name: Wronska, M creators_name: Wang, B creators_name: Irizar, H creators_name: Thygesen, JH creators_name: Bhat, A creators_name: Denaxas, S creators_name: Fatemifar, G creators_name: Finan, C creators_name: Harju-Seppänen, J creators_name: Giannakopoulou, O creators_name: Kuchenbaecker, K creators_name: Zartaloudi, E creators_name: McQuillin, A creators_name: Bramon, E title: The influence of CYP2D6 and CYP2C19 genetic variation on diabetes mellitus risk in people taking antidepressants and antipsychotics ispublished: pub divisions: UCL divisions: B02 divisions: C07 divisions: D79 divisions: D07 divisions: F83 divisions: D14 divisions: GA3 divisions: DD4 divisions: J73 keywords: CYP2C19; CYP2D6; pharmacogenetics; diabetes; personalized medicine; HbA1c; UK Biobank note: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. abstract: CYP2D6 and CYP2C19 enzymes are essential in the metabolism of antidepressants and antipsychotics. Genetic variation in these genes may increase risk of adverse drug reactions. Antidepressants and antipsychotics have previously been associated with risk of diabetes. We examined whether individual genetic differences in CYP2D6 and CYP2C19 contribute to these effects. We identified 31,579 individuals taking antidepressants and 2699 taking antipsychotics within UK Biobank. Participants were classified as poor, intermediate, or normal metabolizers of CYP2D6, and as poor, intermediate, normal, rapid, or ultra-rapid metabolizers of CYP2C19. Risk of diabetes mellitus represented by HbA1c level was examined in relation to the metabolic phenotypes. CYP2D6 poor metabolizers taking paroxetine had higher Hb1Ac than normal metabolizers (mean difference: 2.29 mmol/mol; p < 0.001). Among participants with diabetes who were taking venlafaxine, CYP2D6 poor metabolizers had higher HbA1c levels compared to normal metabolizers (mean differences: 10.15 mmol/mol; p < 0.001. Among participants with diabetes who were taking fluoxetine, CYP2D6 intermediate metabolizers and decreased HbA1c, compared to normal metabolizers (mean difference −7.74 mmol/mol; p = 0.017). We did not observe any relationship between CYP2D6 or CYP2C19 metabolic status and HbA1c levels in participants taking antipsychotic medication. Our results indicate that the impact of genetic variation in CYP2D6 differs depending on diabetes status. Although our findings support existing clinical guidelines, further research is essential to inform pharmacogenetic testing for people taking antidepressants and antipsychotics. date: 2021-11-01 official_url: https://doi.org/10.3390/genes12111758 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1901601 doi: 10.3390/genes12111758 lyricists_name: Bhat, Anjali lyricists_name: Bramon, Elvira lyricists_name: Denaxas, Spyridon lyricists_name: Finan, Christopher lyricists_name: Irizar, Aritz lyricists_name: McQuillin, Andrew lyricists_name: Thygesen, Johan lyricists_id: ABHAT72 lyricists_id: EBRAM47 lyricists_id: SDENA57 lyricists_id: CFINA51 lyricists_id: AIIRI10 lyricists_id: AMCQU28 lyricists_id: JHTHY45 actors_name: Flynn, Bernadette actors_id: BFFLY94 actors_role: owner full_text_status: public publication: Genes volume: 12 number: 11 article_number: 1758 citation: Austin-Zimmerman, I; Wronska, M; Wang, B; Irizar, H; Thygesen, JH; Bhat, A; Denaxas, S; ... Bramon, E; + view all <#> Austin-Zimmerman, I; Wronska, M; Wang, B; Irizar, H; Thygesen, JH; Bhat, A; Denaxas, S; Fatemifar, G; Finan, C; Harju-Seppänen, J; Giannakopoulou, O; Kuchenbaecker, K; Zartaloudi, E; McQuillin, A; Bramon, E; - view fewer <#> (2021) The influence of CYP2D6 and CYP2C19 genetic variation on diabetes mellitus risk in people taking antidepressants and antipsychotics. Genes , 12 (11) , Article 1758. 10.3390/genes12111758 <https://doi.org/10.3390/genes12111758>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10138683/1/genes-12-01758-v4.pdf