The influence of CYP2D6 and CYP2C19 genetic variation on diabetes mellitus risk in people taking antidepressants and antipsychotics
The influence of CYP2D6 and CYP2C19 genetic variation on diabetes mellitus risk in people taking antidepressants and antipsychotics
Abstract BackgroundCYP2D6 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. MethodsWe identified 31,579 individuals taking antidepressants and 2,699 taking antipsychotics within UK Biobank. Participants were classified as poor, intermediate or normal metabolisers of CYP2D6, and as poor, intermediate, normal, rapid and ultra-rapid metabolisers of CYP2C19. Risk of diabetes mellitus represented by HbA1c level was examined in relation to the metabolic phenotypes. We analysed drugs either individually (where sample size permitted) or grouped by class. ResultsCYP2D6 poor metabolisers taking paroxetine had higher Hb1Ac than normal metabolisers (mean difference: 2.29mmol/mol; p < 0.001). Among participants with diabetes who were taking venlafaxine, CYP2D6 poor metabolisers had higher HbA1c levels compared to normal metabolisers (mean differences: 10.15 mmol/mol; p < 0.001. Among participants with diabetes who were taking fluoxetine, we observe that CYP2D6 intermediate metabolisers and decreased HbA1c, compared to normal metabolisers (mean difference ?7.74mmol/mol; p=0.017). We did not observe any relationship between CYP2D6 or CYP2C19 metabolic status and HbA1c levels in participants taking antipsychotic medication. ConclusionOur 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.
Thygesen Johan Hilge、Denaxas Spiros、Harju-Sepp?nen Jasmine、Giannakopoulou Olga、McQuillin Andrew、Wronska Marta、Austin-Zimmerman Isabelle、Wang Baihan、Irizar Haritz、Bramon Elvira、Zartaloudi Eirini、Finan Chris、Kuchenbaecker Karoline、Bhat Anjali、Fatemifar Ghazaleh
Division of Psychiatry, University College London||Institute of Health Informatics, University College LondonInstitute of Health Informatics, University College LondonDivision of Psychiatry, University College LondonDivision of Psychiatry, University College London||Genetics Institute, University College LondonDivision of Psychiatry, University College LondonDivision of Psychiatry, University College LondonDivision of Psychiatry, University College LondonDivision of Psychiatry, University College LondonDivision of Psychiatry, University College London||Department of Genetics & Genomic Sciences, Icahn School of Medicine at Mount SinaiDivision of Psychiatry, University College LondonDivision of Psychiatry, University College LondonInstitute of Cardiovascular Science, Faculty of Population Health, University College London||UCL British Heart Foundation Research Accelerator||Department of Cardiology, Division Heart and Lungs, University Medical Center UtrechtDivision of Psychiatry, University College London||Genetics Institute, University College LondonDivision of Psychiatry, University College LondonInstitute of Health Informatics, University College London
医药卫生理论药学医学研究方法
Thygesen Johan Hilge,Denaxas Spiros,Harju-Sepp?nen Jasmine,Giannakopoulou Olga,McQuillin Andrew,Wronska Marta,Austin-Zimmerman Isabelle,Wang Baihan,Irizar Haritz,Bramon Elvira,Zartaloudi Eirini,Finan Chris,Kuchenbaecker Karoline,Bhat Anjali,Fatemifar Ghazaleh.The influence of CYP2D6 and CYP2C19 genetic variation on diabetes mellitus risk in people taking antidepressants and antipsychotics[EB/OL].(2025-03-28)[2025-06-04].https://www.medrxiv.org/content/10.1101/2021.07.07.21259926.点此复制
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