Analysis of ABCB1 Gene Polymorphisms and Their Impact on Tacrolimus Blood Levels in Kidney Transplant Recipients

Tacrolimus (Tc) is an immunosuppressant used in transplant patients, but its therapeutic range is narrow, making precise dosing essential. This study investigates the association of three single nucleotide polymorphisms (SNPs) (ABCB1 3435C>T, 1236C>T, 2677G>T/A) with Tc levels over time to gain better insights into their role in personalized medicine. We conducted the study over four distinct periods: 1-14 days, 15-30 days, 31-60 days, and beyond 60 days post-transplantation. The analysis included allele, genotype, haplotype, and diplotype frequencies of the three SNPs concerning Tc blood levels. Statistical significance was determined, and false discovery rate (<i>P</i><sub>FDR</sub>) correction was applied where appropriate. Significant associations were found between the C (ABCB1 C1236T), A alleles (ABCB1 G2677T/A), the CAC haplotype and lower Tc levels. The CAC-TGT and TGT-TGT diplotypes significantly influence how patients metabolize the drug. The TGT haplotype and the AA genotype (ABCB1 G2677T/A) were associated with higher Tc levels, suggesting a long-term genetic influence. Genetic factors, specifically certain SNPs and diplotypes, significantly impact Tc blood levels, with their influence varying over time.

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Publication Details

Journal
International Journal of Molecular Sciences
Published
2024-10-12
DOI
https://doi.org/10.3390/ijms252010999
Citations
2
Primary Topic
Drug Transport and Resistance Mechanisms
Type
article
Field-Weighted Citation Impact
0.57
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article

Analysis of ABCB1 Gene Polymorphisms and Their Impact on Tacrolimus Blood Levels in Kidney Transplant Recipients

Ion Mărunțelu, Corina Andreea Rotarescu, Ion Rotarescu, Ileana Constantinescu et al.
2 citations
International Journal of Molecular Sciences
Drug Transport and Resistance Mechanisms
0.57
article

Analysis of ABCB1 Gene Polymorphisms and Their Impact on Tacrolimus Blood Levels in Kidney Transplant Recipients

Ion Mărunțelu, Corina Andreea Rotarescu, Ion Rotarescu, Ileana Constantinescu, Alexandra-Elena Constantinescu
article en
2 citations

Abstract

Tacrolimus (Tc) is an immunosuppressant used in transplant patients, but its therapeutic range is narrow, making precise dosing essential. This study investigates the association of three single nucleotide polymorphisms (SNPs) (ABCB1 3435C>T, 1236C>T, 2677G>T/A) with Tc levels over time to gain better insights into their role in personalized medicine. We conducted the study over four distinct periods: 1-14 days, 15-30 days, 31-60 days, and beyond 60 days post-transplantation. The analysis included allele, genotype, haplotype, and diplotype frequencies of the three SNPs concerning Tc blood levels. Statistical significance was determined, and false discovery rate (<i>P</i><sub>FDR</sub>) correction was applied where appropriate. Significant associations were found between the C (ABCB1 C1236T), A alleles (ABCB1 G2677T/A), the CAC haplotype and lower Tc levels. The CAC-TGT and TGT-TGT diplotypes significantly influence how patients metabolize the drug. The TGT haplotype and the AA genotype (ABCB1 G2677T/A) were associated with higher Tc levels, suggesting a long-term genetic influence. Genetic factors, specifically certain SNPs and diplotypes, significantly impact Tc blood levels, with their influence varying over time.

International Journal of Molecular SciencesVol. 25(20)
Carol Davila University of Medicine and Pharmacy (RO), Academia Oamenilor de Știință din România (RO), Institutul de Urgenţă pentru Boli Cardiovasculare "Prof.Dr. C.C. Iliescu" (RO), Institutul Clinic Fundeni (RO)
Good health and well-being
Openalex Percentile: Top 27%
Drug Transport and Resistance Mechanisms
0.57
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