The pharmacogenetics of tacrolimus in renal transplant patients: association with tremors, new-onset diabetes and other clinical events.

Autor: Abderahmene A; Biochemistry Department, LR12SP11, Sahloul University Hospital, Street Route Ceinture Sahloul, 4054, Sousse, Tunisia. amani.abderahmene@gmail.com.; University of Monastir, Faculty of Pharmacy of Monastir, Street Ibn Sina, 5000, Monastir, Tunisia. amani.abderahmene@gmail.com., Khalij Y; Biochemistry Department, LR12SP11, Sahloul University Hospital, Street Route Ceinture Sahloul, 4054, Sousse, Tunisia.; University of Monastir, Faculty of Pharmacy of Monastir, Street Ibn Sina, 5000, Monastir, Tunisia., Moussa A; Biochemistry Department, LR12SP11, Sahloul University Hospital, Street Route Ceinture Sahloul, 4054, Sousse, Tunisia.; University of Monastir, Faculty of Pharmacy of Monastir, Street Ibn Sina, 5000, Monastir, Tunisia., Ammar M; Biochemistry Department, LR12SP11, Sahloul University Hospital, Street Route Ceinture Sahloul, 4054, Sousse, Tunisia.; University of Monastir, Faculty of Pharmacy of Monastir, Street Ibn Sina, 5000, Monastir, Tunisia., Ellouz A; Biochemistry Department, LR12SP11, Sahloul University Hospital, Street Route Ceinture Sahloul, 4054, Sousse, Tunisia.; University of Monastir, Faculty of Pharmacy of Monastir, Street Ibn Sina, 5000, Monastir, Tunisia., Amor D; Biochemistry Department, LR12SP11, Sahloul University Hospital, Street Route Ceinture Sahloul, 4054, Sousse, Tunisia.; University of Monastir, Faculty of Pharmacy of Monastir, Street Ibn Sina, 5000, Monastir, Tunisia., Abbes H; Biochemistry Department, LR12SP11, Sahloul University Hospital, Street Route Ceinture Sahloul, 4054, Sousse, Tunisia.; University of Monastir, Faculty of Pharmacy of Monastir, Street Ibn Sina, 5000, Monastir, Tunisia., Ganouni MR; Biochemistry Department, LR12SP11, Sahloul University Hospital, Street Route Ceinture Sahloul, 4054, Sousse, Tunisia.; University of Monastir, Faculty of Pharmacy of Monastir, Street Ibn Sina, 5000, Monastir, Tunisia., Sahtout W; Nephrology Department, Sahloul University Hospital, Street Route Ceinture Sahloul, 4054, Sousse, Tunisia., Chouchene S; Hematology Department, Fattouma Bourguiba University Hospital, 5000, Monastir, Tunisia., Omezzine A; Biochemistry Department, LR12SP11, Sahloul University Hospital, Street Route Ceinture Sahloul, 4054, Sousse, Tunisia.; University of Monastir, Faculty of Pharmacy of Monastir, Street Ibn Sina, 5000, Monastir, Tunisia., Zellama D; Nephrology Department, Sahloul University Hospital, Street Route Ceinture Sahloul, 4054, Sousse, Tunisia., Bouslama A; Biochemistry Department, LR12SP11, Sahloul University Hospital, Street Route Ceinture Sahloul, 4054, Sousse, Tunisia.; University of Monastir, Faculty of Pharmacy of Monastir, Street Ibn Sina, 5000, Monastir, Tunisia.
Jazyk: angličtina
Zdroj: The pharmacogenomics journal [Pharmacogenomics J] 2024 Jan 22; Vol. 24 (1), pp. 3. Date of Electronic Publication: 2024 Jan 22.
DOI: 10.1038/s41397-024-00323-4
Abstrakt: Our study is the first study to investigate the effect of SNPs in CYP3A5, CYP3A4, ABCB1 and POR genes on the incidence of tremors, nephrotoxicity, and diabetes mellitus. A total of 223 renal transplant patients receiving tacrolimus and mycophenolate mofetil (MMF) were recruited. Both adults and children patients participated in the study. Genotyping was performed using PROFLEX-PCR followed by RFLP. MPA and tacrolimus plasma concentrations were measured by immunoassay. The AUC0-12h of MMF was estimated by a Bayesian method. We found a statistically significant association between the CYP3A5*3 and CYP3A4*1B genotypes and the tacrolimus exposure. We found a lower occurrence of nephrotoxicity (p = 0.03), tremor (p = 0.01), and new-onset diabetes (p = 0.002) associated with CYP3A5*1 allele. The CYP3A4*1B allele was significantly associated with a lower occurrence of new-onset diabetes (p = 0.026). The CYP3A5*1 allele was significantly associated with an increased risk of acute and chronic rejection (p = 0.03 and p < 0.001, respectively). Our results support the usefulness of tacrolimus pharmacokinetics in pre-kidney transplant assessments.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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