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Predictive role of ITPA genetic variants in thiopurine-related myelotoxicity in Crohn's disease patients.
- Source :
-
The pharmacogenomics journal [Pharmacogenomics J] 2024 Jun 21; Vol. 24 (4), pp. 20. Date of Electronic Publication: 2024 Jun 21. - Publication Year :
- 2024
-
Abstract
- Thiopurines, an effective therapy for Crohn's disease (CD), often lead to adverse events (AEs). Gene polymorphisms affecting thiopurine metabolism may predict AEs. This retrospective study in CD patients (n = 114) with TPMT activity > 5 Units/Red Blood Cells analyzed TPMT (c.238 G > C, c.460 G > A, c.719 A > G), ITPA (c.94 C > A, IVS2 + 21 A > C), and NUDT15 (c.415 C > T) polymorphisms. All patients received azathioprine (median dose 2.2 mg/kg) with 41.2% experiencing AEs, mainly myelotoxicity (28.1%). No NUDT15 polymorphisms were found, 7% had TPMT, and 31.6% had ITPA polymorphisms. AEs led to therapy modifications in 41.2% of patients. Multivariate analysis identified advanced age (OR 1.046, p = 0.007) and ITPA IVS2 + 21 A > C (OR 3.622, p = 0.015) as independent predictors of AEs. IVS2 + 21 A > C was also associated with myelotoxicity (OR 2.863, p = 0.021). These findings suggest that ITPA IVS2 + 21 A > C polymorphism and advanced age predict AEs during thiopurine therapy for CD with intermediate-normal TPMT activity.<br /> (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
- Subjects :
- Humans
Female
Male
Adult
Retrospective Studies
Middle Aged
Young Adult
Immunosuppressive Agents adverse effects
Immunosuppressive Agents therapeutic use
Adolescent
Pharmacogenomic Variants genetics
Polymorphism, Single Nucleotide genetics
Polymorphism, Genetic genetics
Mercaptopurine adverse effects
Mercaptopurine therapeutic use
Multivariate Analysis
Aged
Risk Factors
Nudix Hydrolases
Inosine Triphosphatase
Crohn Disease genetics
Crohn Disease drug therapy
Pyrophosphatases genetics
Azathioprine adverse effects
Azathioprine therapeutic use
Methyltransferases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1473-1150
- Volume :
- 24
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- The pharmacogenomics journal
- Publication Type :
- Academic Journal
- Accession number :
- 38906864
- Full Text :
- https://doi.org/10.1038/s41397-024-00341-2