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CYP3A5 polymorphism in Mexican renal transplant recipients and its association with tacrolimus dosing.
Arch Med Res. 2012 May; 43(4):283-7.AM

Abstract

BACKGROUND AND AIMS

Variability in CYP3A5 expression associated with differences in tacrolimus bioavailability has been documented. The wild-type allele CYP3A5*1 expresses the functional protein, whereas the CYP3A5*3 allele is a splice variant with a premature stop codon and encodes a truncated nonfunctional protein. The aim of the study was to determine the frequency of CYP3A5*1 and CYP3A5*3 in 291 (124 adults, 167 pediatric) Mexican renal transplant recipients, evaluate the tacrolimus dose requirements by genotype and compare genotype frequency data with that of other populations.

METHODS

We carried out a multicenter study. Patients were recruited from three institutions located in Mexico City. Genotyping of the CYP3A5*1 and CYP3A5*3 alleles was performed by direct DNA sequencing.

RESULTS

Eighteen patients (6.2%) were CYP3A5*1*1 homozygous carriers or functional protein expresser homozygous, 121 patients (41.6 %) were CYP3A5*1*3 were heterozygous carriers or heterozygous expressers, and 152 patients (52.2%) were CYP3A5*3*3 homozygous carriers or homozygous nonexpressers. There was a statistically significant difference in frequency of the functional and nonfunctional expresser phenotypes from those reported for Black and Caucasian, but not for South Asian populations. The CYP3A5 phenotype had a significant impact in tacrolimus bioavailability, as wild-type carriers required higher dosing compared to mutated carriers to achieve similar drug trough levels. Patients with CYP3A5*1*1 genotype had a median dose requirement of 0.16 mg/kg/day, CYP3A5*1*3 patients had a median tacrolimus dose of 0.13 mg/kg/day and CYP3A5*3*3 had a median dose of 0.07 mg/kg/day (Kruskal-Wallis, p <0.0001).

CONCLUSIONS

Of the Mexican transplant recipients, 52.2% were CYP3A5*3*3 and required significantly lower tacrolimus dose than those with CYP3A5*1 allele.

Authors+Show Affiliations

Hospital Infantil de México Federico Gómez, Mexico City, Mexico.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22704849

Citation

García-Roca, Pilar, et al. "CYP3A5 Polymorphism in Mexican Renal Transplant Recipients and Its Association With Tacrolimus Dosing." Archives of Medical Research, vol. 43, no. 4, 2012, pp. 283-7.
García-Roca P, Medeiros M, Reyes H, et al. CYP3A5 polymorphism in Mexican renal transplant recipients and its association with tacrolimus dosing. Arch Med Res. 2012;43(4):283-7.
García-Roca, P., Medeiros, M., Reyes, H., Rodríguez-Espino, B. A., Alberú, J., Ortiz, L., Vásquez-Perdomo, M., Elizondo, G., Morales-Buenrostro, L. E., Mancilla Urrea, E., & Castañeda-Hernández, G. (2012). CYP3A5 polymorphism in Mexican renal transplant recipients and its association with tacrolimus dosing. Archives of Medical Research, 43(4), 283-7. https://doi.org/10.1016/j.arcmed.2012.05.005
García-Roca P, et al. CYP3A5 Polymorphism in Mexican Renal Transplant Recipients and Its Association With Tacrolimus Dosing. Arch Med Res. 2012;43(4):283-7. PubMed PMID: 22704849.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CYP3A5 polymorphism in Mexican renal transplant recipients and its association with tacrolimus dosing. AU - García-Roca,Pilar, AU - Medeiros,Mara, AU - Reyes,Herlinda, AU - Rodríguez-Espino,Benjamín Antonio, AU - Alberú,Josefina, AU - Ortiz,Lourdes, AU - Vásquez-Perdomo,Mayela, AU - Elizondo,Guillermo, AU - Morales-Buenrostro,Luis Eduardo, AU - Mancilla Urrea,Eduardo, AU - Castañeda-Hernández,Gilberto, Y1 - 2012/06/13/ PY - 2012/02/23/received PY - 2012/04/23/accepted PY - 2012/6/19/entrez PY - 2012/6/19/pubmed PY - 2012/12/10/medline SP - 283 EP - 7 JF - Archives of medical research JO - Arch Med Res VL - 43 IS - 4 N2 - BACKGROUND AND AIMS: Variability in CYP3A5 expression associated with differences in tacrolimus bioavailability has been documented. The wild-type allele CYP3A5*1 expresses the functional protein, whereas the CYP3A5*3 allele is a splice variant with a premature stop codon and encodes a truncated nonfunctional protein. The aim of the study was to determine the frequency of CYP3A5*1 and CYP3A5*3 in 291 (124 adults, 167 pediatric) Mexican renal transplant recipients, evaluate the tacrolimus dose requirements by genotype and compare genotype frequency data with that of other populations. METHODS: We carried out a multicenter study. Patients were recruited from three institutions located in Mexico City. Genotyping of the CYP3A5*1 and CYP3A5*3 alleles was performed by direct DNA sequencing. RESULTS: Eighteen patients (6.2%) were CYP3A5*1*1 homozygous carriers or functional protein expresser homozygous, 121 patients (41.6 %) were CYP3A5*1*3 were heterozygous carriers or heterozygous expressers, and 152 patients (52.2%) were CYP3A5*3*3 homozygous carriers or homozygous nonexpressers. There was a statistically significant difference in frequency of the functional and nonfunctional expresser phenotypes from those reported for Black and Caucasian, but not for South Asian populations. The CYP3A5 phenotype had a significant impact in tacrolimus bioavailability, as wild-type carriers required higher dosing compared to mutated carriers to achieve similar drug trough levels. Patients with CYP3A5*1*1 genotype had a median dose requirement of 0.16 mg/kg/day, CYP3A5*1*3 patients had a median tacrolimus dose of 0.13 mg/kg/day and CYP3A5*3*3 had a median dose of 0.07 mg/kg/day (Kruskal-Wallis, p <0.0001). CONCLUSIONS: Of the Mexican transplant recipients, 52.2% were CYP3A5*3*3 and required significantly lower tacrolimus dose than those with CYP3A5*1 allele. SN - 1873-5487 UR - https://www.unboundmedicine.com/medline/citation/22704849/CYP3A5_polymorphism_in_Mexican_renal_transplant_recipients_and_its_association_with_tacrolimus_dosing_ DB - PRIME DP - Unbound Medicine ER -