Effects of CYP2D6*10 Mutation on Binding Affinity on Common Antidepressants in Japan
by Miu Nakajima
Abstract – In Japan, there is an apparent lack of development and stigma associated with mental health treatment, including the use of antidepressants. Additionally, there is a large portion of the population possessing the allelic variant CYP2D6*10, which is part of the Cytochrome P450 superfamily responsible for metabolizing a wide variety of pharmaceuticals. Through this study, we aim to clarify the effects of genetic variation of CYP2D6 on adverse effects when using different antidepressants. We conducted an in silico study of binding affinities of different ligands to two CYP2D6 wild-type models, 4WNW and 2F9Q, and their respective threaded *10 models. Using SwissDock, the 4WNW model showed that the *10 variant had a lower binding affinity as compared to the wild-type. When using the 2F9Q model or X-Score, we had inconsistent results, leading us to question the reliability of these resources. Our results from SwissDock suggest that the *10 variant has a lower binding affinity, and therefore leading to a lower rate of metabolism. This suggests that people with this genetic mutation may be more susceptible to adverse effects when using antidepressants. Furthermore, future experiments regarding the correlation between CYP2D6*10 and drug metabolism should be conducted to advance mental health treatment and personalized medicine in Japan.
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