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Association between CYP2D6 phenotype and recurrence of Plasmodium vivax infection in south Korean patients

BACKGROUND: Primaquine is activated by CYP2D6 in the hepatocytes. In Korea, primaquine is the only hypnozoitocidal agent used for patients with vivax malaria. Thus, patients with poor CYP2D6 activity could have an increased risk of primaquine failure and subsequent relapse. The study sought to ident...

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Autores principales: Choi, Sungim, Choi, Heun, Park, Seong Yeon, Kwak, Yee Gyung, Song, Je Eun, Shin, So Youn, Baek, Ji Hyeon, Shin, Hyun-IL, Cho, Shin-Hyung, Lee, Sang-Eun, Kwon, Jeong-Ran, Park, Sookkyung, Kim, Miyoung, Oh, Hong Sang, Kim, Yong Chan, Kim, Min Jae, Yeom, Joon-Sup
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9552356/
https://www.ncbi.nlm.nih.gov/pubmed/36217154
http://dx.doi.org/10.1186/s12936-022-04311-6
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author Choi, Sungim
Choi, Heun
Park, Seong Yeon
Kwak, Yee Gyung
Song, Je Eun
Shin, So Youn
Baek, Ji Hyeon
Shin, Hyun-IL
Cho, Shin-Hyung
Lee, Sang-Eun
Kwon, Jeong-Ran
Park, Sookkyung
Kim, Miyoung
Oh, Hong Sang
Kim, Yong Chan
Kim, Min Jae
Yeom, Joon-Sup
author_facet Choi, Sungim
Choi, Heun
Park, Seong Yeon
Kwak, Yee Gyung
Song, Je Eun
Shin, So Youn
Baek, Ji Hyeon
Shin, Hyun-IL
Cho, Shin-Hyung
Lee, Sang-Eun
Kwon, Jeong-Ran
Park, Sookkyung
Kim, Miyoung
Oh, Hong Sang
Kim, Yong Chan
Kim, Min Jae
Yeom, Joon-Sup
author_sort Choi, Sungim
collection PubMed
description BACKGROUND: Primaquine is activated by CYP2D6 in the hepatocytes. In Korea, primaquine is the only hypnozoitocidal agent used for patients with vivax malaria. Thus, patients with poor CYP2D6 activity could have an increased risk of primaquine failure and subsequent relapse. The study sought to identify the association between CYP2D6 phenotype and recurrence of malaria in Korean patients. METHODS: A total of 102 patients with vivax malaria were prospectively enrolled from eight institutions in Korea. An additional 38 blood samples from patients with recurred vivax malaria were provided by the Korea Disease Control and Prevention Agency. Malaria recurrence was defined as more than one episode of vivax malaria in the same or consecutive years. CYP2D6 star alleles, phenotypes, and activity scores were examined. RESULTS: Genotyping for CYP2D6 was successful in 101 of the prospectively enrolled patients and 38 samples from the Korea Disease Control and Prevention Agency, of which 91 were included in the no-recurrence group and 48 were included in the recurrence group. Reduced CYP2D6 activity (intermediate metabolizer) phenotype was more common in the recurrence group than in the no-recurrence group (OR, 2.33 (95% CI, 1.14–4.77); p = 0.02). Patients with lower CYP2D6 activity had a higher probability of recurrence (p = 0.029). CONCLUSION: This study suggests that CYP2D6 polymorphism may affect primaquine efficacy and thus Plasmodium vivax recurrence in Korea. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12936-022-04311-6.
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spelling pubmed-95523562022-10-12 Association between CYP2D6 phenotype and recurrence of Plasmodium vivax infection in south Korean patients Choi, Sungim Choi, Heun Park, Seong Yeon Kwak, Yee Gyung Song, Je Eun Shin, So Youn Baek, Ji Hyeon Shin, Hyun-IL Cho, Shin-Hyung Lee, Sang-Eun Kwon, Jeong-Ran Park, Sookkyung Kim, Miyoung Oh, Hong Sang Kim, Yong Chan Kim, Min Jae Yeom, Joon-Sup Malar J Research BACKGROUND: Primaquine is activated by CYP2D6 in the hepatocytes. In Korea, primaquine is the only hypnozoitocidal agent used for patients with vivax malaria. Thus, patients with poor CYP2D6 activity could have an increased risk of primaquine failure and subsequent relapse. The study sought to identify the association between CYP2D6 phenotype and recurrence of malaria in Korean patients. METHODS: A total of 102 patients with vivax malaria were prospectively enrolled from eight institutions in Korea. An additional 38 blood samples from patients with recurred vivax malaria were provided by the Korea Disease Control and Prevention Agency. Malaria recurrence was defined as more than one episode of vivax malaria in the same or consecutive years. CYP2D6 star alleles, phenotypes, and activity scores were examined. RESULTS: Genotyping for CYP2D6 was successful in 101 of the prospectively enrolled patients and 38 samples from the Korea Disease Control and Prevention Agency, of which 91 were included in the no-recurrence group and 48 were included in the recurrence group. Reduced CYP2D6 activity (intermediate metabolizer) phenotype was more common in the recurrence group than in the no-recurrence group (OR, 2.33 (95% CI, 1.14–4.77); p = 0.02). Patients with lower CYP2D6 activity had a higher probability of recurrence (p = 0.029). CONCLUSION: This study suggests that CYP2D6 polymorphism may affect primaquine efficacy and thus Plasmodium vivax recurrence in Korea. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12936-022-04311-6. BioMed Central 2022-10-10 /pmc/articles/PMC9552356/ /pubmed/36217154 http://dx.doi.org/10.1186/s12936-022-04311-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Choi, Sungim
Choi, Heun
Park, Seong Yeon
Kwak, Yee Gyung
Song, Je Eun
Shin, So Youn
Baek, Ji Hyeon
Shin, Hyun-IL
Cho, Shin-Hyung
Lee, Sang-Eun
Kwon, Jeong-Ran
Park, Sookkyung
Kim, Miyoung
Oh, Hong Sang
Kim, Yong Chan
Kim, Min Jae
Yeom, Joon-Sup
Association between CYP2D6 phenotype and recurrence of Plasmodium vivax infection in south Korean patients
title Association between CYP2D6 phenotype and recurrence of Plasmodium vivax infection in south Korean patients
title_full Association between CYP2D6 phenotype and recurrence of Plasmodium vivax infection in south Korean patients
title_fullStr Association between CYP2D6 phenotype and recurrence of Plasmodium vivax infection in south Korean patients
title_full_unstemmed Association between CYP2D6 phenotype and recurrence of Plasmodium vivax infection in south Korean patients
title_short Association between CYP2D6 phenotype and recurrence of Plasmodium vivax infection in south Korean patients
title_sort association between cyp2d6 phenotype and recurrence of plasmodium vivax infection in south korean patients
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9552356/
https://www.ncbi.nlm.nih.gov/pubmed/36217154
http://dx.doi.org/10.1186/s12936-022-04311-6
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