Influence of cyp3a5 polymorphism on tacrolimus drug dosing in indian renal allograft recipients: initial experience

Patel et al. Molecular Cytogenetics 2014, 7(Suppl 1):P98http://www.molecularcytogenetics.org/content/7/S1/P98 Influence of CYP3A5 polymorphism on tacrolimusdrug dosing in Indian renal allograft recipients:initial experience Mohan Patel1*, Manoj Gumber1, Vivek Kute1, Pankaj Shah1, Himanushu Patel1, Hargovind Trivedi1, Aruna Vanikar2,Jayesh Sheth3 From International Conference on Human Genetics and 39th Annual Meeting of the Indian Society ofHuman Genetics (ISHG)Ahmadabad, India. 23-25 January 2013 20 patients 16 were found to have CYP3A5 homozygous Tacrolimus (Tac) is the mainstay of standard immunosup- status (A3986G polymorphism in CYP3A5*3 gene-wild pressive regime in renal transplantation today. However, it allele) and 4 with heterozygous status. Patients of CYP3A5 needs regular drug level monitoring in view of narrow homozygous status had mean Tac level of 16.84 ng/dL, therapeutic window to keep blood level in therapeutic median of 15.5 ng/dL (range- 13.2-25 ng/dL) on 7th day of range. The objective of the study was to assess the poten- transplant. So Tac dose was reduced to achieve TDL and tial influence of a functional polymorphism in CYP3A5*3 mean Tac level at 30th day of transplant was 6.6 ng/dL gene on dose requirements and trough blood levels of and median of 7.4 ng/dL (range- 5.5-12.5 ng/dL). At 6th month and 12th month of transplant, mean Tac levelswere 6.1 ng/dL and 5.9 ng/dL. In patients having CYP3A5 homozygous status, mean and median Tac dose after 4 This prospective observational study included 20 weeks was 0.03 mg/kg/day (range- 0.008 to 0.05 mg/kg/ patients of end stage renal disease who underwent renal day) and mean creatinine was 1.17 mg/dL (range-0.8 to transplantion and a follow up of 1 year at our hospital.
1.4 mg/dL) after 30th day. Remaining 4 patients having All the patients were started on standard immunosuppres- CYP3A5 heterozygous status were maintaining TDL at sive regime of Tacrolimus-Mycophenolate mofetil along Tac dose of 0.06 mg/kg/day. Five patients had graft biopsy with steroids with a starting dose of Tac 0.08 mg/kg/day.
during first 4 weeks of renal transplant showing acute Genotype of CYP3A5 was studied in 20 patients requiring tubular necrosis (ATN) in three patients, acute cellular low dose of Tac. At 7th and 30th day, and 3 monthly after rejection in one patient and cellular rejection with evidence transplant, Tac dosages (mg/kg/d), were adjusted based on of calcineurine inhibitor (CNI) toxicity in one patient.
blood levels and complications. Polymerase chain reaction,followed by restriction fragment length polymorphism analysis was used for genotyping CYP3A5*3 gene This study demonstrates the usefulness of CYP3A5 genotype in transplant patients taking Tacrolimus-Mycophenolate mofetil and also shows that majority of our patients carry mutant allele A3986G in CYP3A5*3 gene.
Out of 20 patients (17 males and 3 females) included inthe study, 16 had live related renal transplantation and 4 had diseased donor renal transplantation. Out of 1Department of Nephrology and Clinical Transplantation, Institute of KidneyDiseases and Research Center, Dr HL Trivedi Institute of Transplantation Sciences, Ahmedabad, India. 2Department of Pathology and Department of Nephrology and Clinical Transplantation, Institute of Kidney Immunohematology, IKDRC-ITS, Ahmedabad, India. 3Foundation for Research Diseases and Research Center, Dr HL Trivedi Institute of Transplantation in Genetics and Endocrinology (FRIGE) Institute Of Human Genetics, Full list of author information is available at the end of the article 2014 Patel et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License ), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (applies to the data made available in this article, unless otherwise stated.
Patel et al. Molecular Cytogenetics 2014, 7(Suppl 1):P98 http://www.molecularcytogenetics.org/content/7/S1/P98 doi:10.1186/1755-8166-7-S1-P98Cite this article as: Patel et al.: Influence of CYP3A5 polymorphism ontacrolimus drug dosing in Indian renal allograft recipients: initialexperience. Molecular Cytogenetics 2014 7(Suppl 1):P98.
Submit your next manuscript to BioMed Central
and take full advantage of:
• Convenient online submission
• Thorough peer review
• No space constraints or color figure charges
• Immediate publication on acceptance
• Inclusion in PubMed, CAS, Scopus and Google Scholar
• Research which is freely available for redistribution
Submit your manuscript at www.biomedcentral.com/submit

Source: http://www.molecularcytogenetics.org/content/pdf/1755-8166-7-S1-P98.pdf