Implementation of NUDT15 Genotyping to Prevent Azathioprine-Induced Leukopenia for Patients With Autoimmune Disorders in Chinese Population.

Humans Azathioprine / adverse effects Prospective Studies Genotype Pyrophosphatases / genetics Leukopenia / chemically induced Immunosuppressive Agents / adverse effects Autoimmune Diseases / chemically induced Thrombocytopenia Methyltransferases / genetics

Journal

Clinical pharmacology and therapeutics
ISSN: 1532-6535
Titre abrégé: Clin Pharmacol Ther
Pays: United States
ID NLM: 0372741

Informations de publication

Date de publication:
11 2022
Historique:
received: 29 04 2022
accepted: 13 07 2022
pubmed: 24 7 2022
medline: 25 10 2022
entrez: 23 7 2022
Statut: ppublish

Résumé

Azathioprine (AZA) is commonly used for many autoimmune disorders; however, the limitation of its clinical use is due to potential toxicities, including severe leukopenia. Recent studies have identified genetic NUDT15 variants strongly associated with AZA-induced leukopenia in Asian patients. This study aimed to investigate the strength of above genetic association and evaluate the usefulness of prospective screening of the NUDT15 variants to prevent AZA-induced leukopenia in Chinese patients. AZA-induced leukopenia in patients with autoimmune disorders were enrolled from multiple medical centers in Taiwan/China between 2012 and 2017 to determine the strength of genetic association of NUDT15 or TPMT variants by whole exome sequencing (WES). Furthermore, a prospective study was conducted between 2018 and 2021 to investigate the incidence of AZA-induced leukopenia with and without genetic screening. The WES result showed the genetic variants of NUDT15 R139C (rs116855232) (P = 3.7 × 10

Identifiants

DOI: 10.1002/cpt.2716 PMID: 35869597 PMC: PMC9804440
pubmed: 35869597
doi: 10.1002/cpt.2716
pmc: PMC9804440
doi:

Substances chimiques

Azathioprine MRK240IY2L
Pyrophosphatases EC 3.6.1.-
Immunosuppressive Agents 0
Methyltransferases EC 2.1.1.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1079-1087

Informations de copyright

© 2022 Chang Gung Memorial Hospital. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.

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Auteurs

Chuang-Wei Wang (CW)

Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei and Keelung, Taiwan.
Cancer Vaccine and Immune Cell Therapy Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taiwan.
Chang Gung Immunology Consortium, Chang Gung Memorial Hospital Chang Gung University, Taoyuan, Taiwan.
Department of Dermatology, Xiamen Chang Gung Hospital, Xiamen, China.
College of Medicine, Chang Gung University, Taoyuan, Taiwan.
ORCID: 0000-0002-7921-4129

Min-Hui Chi (MH)

Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei and Keelung, Taiwan.
College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
ORCID: 0000-0001-5774-2775

Tsen-Fang Tsai (TF)

Department of Dermatology, National Taiwan University Hospital, Taipei, Taiwan.
Department of Dermatology, National Taiwan University College of Medicine, Taipei, Taiwan.

Kuang-Hui Yu (KH)

College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Division of Rheumatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Taiwan.

Hsiao-Wen Kao (HW)

College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Taiwan.

Hsiang-Cheng Chen (HC)

Division of Rheumatology, Immunology and Allergy, Department of Medicine, Tri-Service General Hospital, Taipei, Taiwan.

Chun-Bing Chen (CB)

Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei and Keelung, Taiwan.
Chang Gung Immunology Consortium, Chang Gung Memorial Hospital Chang Gung University, Taoyuan, Taiwan.
Department of Dermatology, Xiamen Chang Gung Hospital, Xiamen, China.
College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung, Taiwan.
Immune-Oncology Center of Excellence, Chang Gung Memorial Hospital, Linkou, Taiwan.
Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
ORCID: 0000-0002-7378-4235

Chun-Wei Lu (CW)

Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei and Keelung, Taiwan.
Department of Dermatology, Xiamen Chang Gung Hospital, Xiamen, China.
College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Immune-Oncology Center of Excellence, Chang Gung Memorial Hospital, Linkou, Taiwan.
Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
ORCID: 0000-0002-9341-4012

Wei-Ti Chen (WT)

Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei and Keelung, Taiwan.
Department of Dermatology, Xiamen Chang Gung Hospital, Xiamen, China.
College of Medicine, Chang Gung University, Taoyuan, Taiwan.
ORCID: 0000-0002-2342-045X

Ya-Ching Chang (YC)

Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei and Keelung, Taiwan.
College of Medicine, Chang Gung University, Taoyuan, Taiwan.

Chih-Jung Chang (CJ)

Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei and Keelung, Taiwan.
Medical Research Center and Xiamen Chang Gung Allergology Consortium, Xiamen Chang Gung Hospital, Xiamen, Fujian, China.
School of Medicine, Huaqiao University, Quanzhou, Fujian, China.

Yun-Ting Chang (YT)

Department of Dermatology, Taipei Veterans General Hospital, Taipei, Taiwan.

Yeong-Jian Jan Wu (YJ)

College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Division of Allergy, Immunology and Rheumatology, Department of Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan.

Chee-Jen Chang (CJ)

Research Services Center for Health Information, Chang Gung University, Taoyuan, Taiwan.

Yu Huei Huang (YH)

Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei and Keelung, Taiwan.
College of Medicine, Chang Gung University, Taoyuan, Taiwan.

Chau-Yee Ng (CY)

Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei and Keelung, Taiwan.
College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.

Po-Wei Huang (PW)

Department of Dermatology, National Taiwan University Hospital, Taipei, Taiwan.
Department of Dermatology, National Taiwan University College of Medicine, Taipei, Taiwan.
Section of Dermatology, Department of Surgery, National Taiwan University Cancer Center, Taipei, Taiwan.
ORCID: 0000-0002-1360-7149

Yu-Jr Lin (YJ)

Research Services Center for Health Information, Chang Gung University, Taoyuan, Taiwan.

Rosaline Chung-Yee Hui (RC)

Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei and Keelung, Taiwan.
College of Medicine, Chang Gung University, Taoyuan, Taiwan.

Wen-Hung Chung (WH)

Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei and Keelung, Taiwan.
Cancer Vaccine and Immune Cell Therapy Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taiwan.
Chang Gung Immunology Consortium, Chang Gung Memorial Hospital Chang Gung University, Taoyuan, Taiwan.
Department of Dermatology, Xiamen Chang Gung Hospital, Xiamen, China.
College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung, Taiwan.
Immune-Oncology Center of Excellence, Chang Gung Memorial Hospital, Linkou, Taiwan.
Department of Dermatology, Beijing Tsinghua Chang Gung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.
Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Genomic Medicine Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taiwan.
ORCID: 0000-0003-1681-0959

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Implementation of NUDT15 Genotyping to Prevent...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Nucléosides › Thionucléosides › Azathioprine › Implementation of NUDT15 Genotyping to Prevent...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études prospectives › Implementation of NUDT15 Genotyping to Prevent...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Implementation of NUDT15 Genotyping to Prevent...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Acid anhydride hydrolases › Pyrophosphatases › Implementation of NUDT15 Genotyping to Prevent...
questionsmedicales.fr › Hémopathies et maladies lymphatiques › Hémopathies › Troubles leucocytaires › Leucopénie › Implementation of NUDT15 Genotyping to Prevent...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Effets physiologiques des médicaments › Facteurs immunologiques › Immunosuppresseurs › Implementation of NUDT15 Genotyping to Prevent...
questionsmedicales.fr › Maladies du système immunitaire › Maladies auto-immunes › Implementation of NUDT15 Genotyping to Prevent...
questionsmedicales.fr › Hémopathies et maladies lymphatiques › Hémopathies › Anomalies des plaquettes › Thrombopénie › Implementation of NUDT15 Genotyping to Prevent...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › One-carbon group transferases › Methyltransferases › Implementation of NUDT15 Genotyping to Prevent...