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