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Association study of ABCB1 and CYP3A5 gene polymorphisms with sirolimus trough concentration and dose requirements in Chinese renal transplant recipients.
Biopharm Drug Dispos. 2008 Jan; 29(1):1-5.BD

Abstract

The objective of this study was to investigate the possible association of the ABCB1 gene C3435 T polymorphism and the CYP3A5 gene A6986G polymorphism with sirolimus (SRL) trough concentration and dose requirements in Chinese stable renal transplant recipients. Blood samples were collected from 105 healthy volunteers and 50 renal transplant patients, whose polymorphisms of the ABCB1 and CYP3A5 genes were determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). Plasma concentrations of SRL were determined with HPLC. The allele frequencies of the ABCB1 mutation in Chinese healthy volunteers and renal transplant recipients were 51.0% and 44.0% (p>0.05), while the allele frequencies of the CYP3A5 mutation were 72.9% and 71.0% (p>0.05). The SRL concentration/dose ratio (C/D) in patients with CYP3A5 (*)3/(*)3 were significantly higher than that of those with (*)1 allele (p<0.05). However, no significant differences were observed between C/D and ABCB1 SNPs (p>0.05). These results confirm that when treated with a SRL-based therapy and low-dose steroids, patients carrying the CYP3A5(*)1 allele required significantly more SRL to achieve adequate blood trough concentrations. In patients with SRL-based therapy, genotyping of the CYP3A5 genes may help to optimize the SRL management in renal transplant recipients.

Authors+Show Affiliations

Clinical Pharmacology Research Laboratory, The First Affiliated Hospital of Soochow University, Suzhou 215006, China. miaolysuzhou@163.comNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17941052

Citation

Miao, Li-Yan, et al. "Association Study of ABCB1 and CYP3A5 Gene Polymorphisms With Sirolimus Trough Concentration and Dose Requirements in Chinese Renal Transplant Recipients." Biopharmaceutics & Drug Disposition, vol. 29, no. 1, 2008, pp. 1-5.
Miao LY, Huang CR, Hou JQ, et al. Association study of ABCB1 and CYP3A5 gene polymorphisms with sirolimus trough concentration and dose requirements in Chinese renal transplant recipients. Biopharm Drug Dispos. 2008;29(1):1-5.
Miao, L. Y., Huang, C. R., Hou, J. Q., & Qian, M. Y. (2008). Association study of ABCB1 and CYP3A5 gene polymorphisms with sirolimus trough concentration and dose requirements in Chinese renal transplant recipients. Biopharmaceutics & Drug Disposition, 29(1), 1-5.
Miao LY, et al. Association Study of ABCB1 and CYP3A5 Gene Polymorphisms With Sirolimus Trough Concentration and Dose Requirements in Chinese Renal Transplant Recipients. Biopharm Drug Dispos. 2008;29(1):1-5. PubMed PMID: 17941052.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association study of ABCB1 and CYP3A5 gene polymorphisms with sirolimus trough concentration and dose requirements in Chinese renal transplant recipients. AU - Miao,Li-Yan, AU - Huang,Chen-Rong, AU - Hou,Jian-Quan, AU - Qian,Mei-Ying, PY - 2007/10/18/pubmed PY - 2008/4/11/medline PY - 2007/10/18/entrez SP - 1 EP - 5 JF - Biopharmaceutics & drug disposition JO - Biopharm Drug Dispos VL - 29 IS - 1 N2 - The objective of this study was to investigate the possible association of the ABCB1 gene C3435 T polymorphism and the CYP3A5 gene A6986G polymorphism with sirolimus (SRL) trough concentration and dose requirements in Chinese stable renal transplant recipients. Blood samples were collected from 105 healthy volunteers and 50 renal transplant patients, whose polymorphisms of the ABCB1 and CYP3A5 genes were determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). Plasma concentrations of SRL were determined with HPLC. The allele frequencies of the ABCB1 mutation in Chinese healthy volunteers and renal transplant recipients were 51.0% and 44.0% (p>0.05), while the allele frequencies of the CYP3A5 mutation were 72.9% and 71.0% (p>0.05). The SRL concentration/dose ratio (C/D) in patients with CYP3A5 (*)3/(*)3 were significantly higher than that of those with (*)1 allele (p<0.05). However, no significant differences were observed between C/D and ABCB1 SNPs (p>0.05). These results confirm that when treated with a SRL-based therapy and low-dose steroids, patients carrying the CYP3A5(*)1 allele required significantly more SRL to achieve adequate blood trough concentrations. In patients with SRL-based therapy, genotyping of the CYP3A5 genes may help to optimize the SRL management in renal transplant recipients. SN - 0142-2782 UR - https://www.unboundmedicine.com/medline/citation/17941052/Association_study_of_ABCB1_and_CYP3A5_gene_polymorphisms_with_sirolimus_trough_concentration_and_dose_requirements_in_Chinese_renal_transplant_recipients_ DB - PRIME DP - Unbound Medicine ER -