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Background: This study examines the impact of CYP3A4 and CYP 3A5 genotypes on tacrolimus (Tac) pharmacokinetics in Romanian kidney transplanted patients. Methods: We included 112 kidney recipients genotyped for CYP3A5*3, CYP3A4*1.001, and CYP3A4*22. Patients were categorized into poor, intermediate, rapid, and ultra-rapid metabolizers based on the functional defects linked to CYP3A variants. Results: Predominantly male (63.4%) with an average age of 40.58 years, the cohort exhibited a high prevalence of the CYP3A4*1/*1 (86.6%) and CYP3A5*3/*3 (77.7%) genotypes. CYP3A4*1.001 and CYP3A5*1 alleles significantly influenced the Tac concentration-to-dose (C0/D) ratio in various post-transplant periods, while the CYP3A4*22 allele showed no such effect (p = 0.016, p < 0.001). Stepwise regression highlighted the CYP3A4*1.001's impact in early post-transplant phases, with hematocrit and age also influencing Tac variability. Conclusions: The study indicates a complex interaction of CYP3A4 and CYP3A5 genotypes on Tac metabolism, suggesting the necessity for personalized medication approaches based on genetic profiling in kidney transplant recipients.
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BACKGROUND AND OBJECTIVES: The implications of the genetic component in the initiation and development of chronic lymphoproliferative disorders have been the subject of intense research efforts. Some of the most important genes involved in the occurrence and evolution of these pathologies are the HLA genes. The aim of this study is to analyze, for the first time, possible associations between chronic lymphoproliferative diseases and certain HLA alleles in the Romanian population. MATERIALS AND METHODS: This study included 38 patients with chronic lymphoproliferative disorders, diagnosed between 2021 and 2022 at Fundeni Clinical Institute, Bucharest, Romania, and 50 healthy controls. HLA class I and class II genes (HLA-A/B/C, HLA-DQB1/DPB1/DRB1) were investigated by doing high resolution genotyping using sequence specific primers (SSP). RESULTS: Several HLA alleles were strongly associated with chronic lymphoproliferative disorders. The most important finding was that the HLA-C*02:02 (p = 0.002, OR = 1.101), and HLA-C*12:02 (p = 0.002, OR = 1.101) have a predisposing role in the development of chronic lymphoproliferative disorders. Moreover, we identified that HLA-A*11:01 (p = 0.01, OR = 0.16), HLA-B*35:02 (p = 0.037, OR = 0.94), HLA-B*81:01 (p = 0.037, OR = 0.94), HLA-C*07:02 (p = 0.036, OR = 0.34), HLA-DRB1*11:01 (p = 0.021, OR = 0.19), and HLA-DRB1*13:02 (p = 0.037, OR = 0.94), alleles have protective roles. CONCLUSIONS: Our study indicates that HLA-C*02:02 and HLA-C*12:02 are positively associated with chronic lymphoproliferative disorders for our Romanian patients while HLA-DRB1*11:01, HLA-DRB1*13:02, and HLA-B*35:02 alleles have a protective role against these diseases.