PMID- 37959208
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231117
IS  - 2077-0383 (Print)
IS  - 2077-0383 (Electronic)
IS  - 2077-0383 (Linking)
VI  - 12
IP  - 21
DP  - 2023 Oct 25
TI  - The Role of Pharmacogenetics in the Therapeutic Response to Thiopurines in the 
      Treatment of Inflammatory Bowel Disease: A Systematic Review.
LID - 10.3390/jcm12216742 [doi]
LID - 6742
AB  - This study focuses on the use of thiopurines for treating inflammatory bowel 
      diseases (IBD). These drugs undergo enzymatic changes within the body, resulting 
      in active and inactive metabolites that influence their therapeutic effects. The 
      research examines the role of genetic polymorphisms in the enzyme thiopurine 
      S-methyltransferase (TPMT) in predicting the therapeutic response and adverse 
      effects of thiopurine treatment. The TPMT genotype variations impact the 
      individual responses to thiopurines. Patients with reduced TPMT activity are more 
      susceptible to adverse reactions (AEs), such leukopenia, hepatotoxicity, 
      pancreatitis, and nausea, which are common adverse effects of thiopurine therapy. 
      The therapeutic monitoring of the metabolites 6-thioguanine nucleotides (6-TGN) 
      and 6-methyl mercaptopurine (6-MMP) is proposed to optimize treatment and 
      minimize AEs. Patients with higher 6-TGN levels tend to have better clinical 
      responses, while elevated 6-MMP levels are linked to hepatotoxicity. Genotyping 
      for TPMT before or during treatment initiation is suggested to tailor dosing 
      strategies and enhance treatment efficacy while reducing the risk of 
      myelosuppression. In conclusion, this study highlights the importance of 
      considering genetic variations and metabolite levels in optimizing thiopurine 
      therapy for IBD patients, focusing on balance therapeutic efficacy with the 
      prevention of adverse effects and contributing to personalized treatment and 
      better patient outcomes.
FAU - Ribeiro, Aline C
AU  - Ribeiro AC
AD  - Department of Pharmaceutical Sciences, Faculty of Pharmacy, Federal University of 
      Juiz de Fora, Juiz de Fora 36036-900, Minas Gerais, Brazil.
FAU - Gerheim, Pamela S A S
AU  - Gerheim PSAS
AD  - Department of Pharmacology, Federal University of Juiz de Fora, Juiz de Fora 
      36036-900, Minas Gerais, Brazil.
FAU - Chebli, Julio Maria Fonseca
AU  - Chebli JMF
AD  - Division of Gastroenterology, Department of Internal Medicine, Federal University 
      of Juiz de Fora, Juiz de Fora 36036-900, Minas Gerais, Brazil.
FAU - Nascimento, Jorge Willian L
AU  - Nascimento JWL
AUID- ORCID: 0000-0002-0334-0217
AD  - Laboratory of Clinical and Experimental Pharmacology, Department of Pharmacology, 
      Federal University of Juiz de Fora, Juiz de Fora 36036-900, Minas Gerais, Brazil.
FAU - de Faria Pinto, Priscila
AU  - de Faria Pinto P
AUID- ORCID: 0000-0002-9011-2027
AD  - Department of Biochemistry, Institute of Biological Sciences, Federal University 
      of Juiz de Fora, Juiz de Fora 36036-900, Minas Gerais, Brazil.
LA  - eng
GR  - APQ-03823-17/Fundacao de Amparo a Pesquisa do Estado de Minas Gerais/
PT  - Journal Article
PT  - Review
DEP - 20231025
PL  - Switzerland
TA  - J Clin Med
JT  - Journal of clinical medicine
JID - 101606588
PMC - PMC10649589
OTO - NOTNLM
OT  - 6-mercaptopurine
OT  - azathioprine
OT  - inflammatory bowel diseases
OT  - pharmacogenetics
OT  - thiopurine S-methyl transferase
COIS- The authors declare no conflict of interest.
EDAT- 2023/11/14 06:42
MHDA- 2023/11/14 06:43
PMCR- 2023/10/25
CRDT- 2023/11/14 02:12
PHST- 2023/09/04 00:00 [received]
PHST- 2023/09/26 00:00 [revised]
PHST- 2023/10/07 00:00 [accepted]
PHST- 2023/11/14 06:43 [medline]
PHST- 2023/11/14 06:42 [pubmed]
PHST- 2023/11/14 02:12 [entrez]
PHST- 2023/10/25 00:00 [pmc-release]
AID - jcm12216742 [pii]
AID - jcm-12-06742 [pii]
AID - 10.3390/jcm12216742 [doi]
PST - epublish
SO  - J Clin Med. 2023 Oct 25;12(21):6742. doi: 10.3390/jcm12216742.