Tacrolimus pharmacogenetics: the CYP3A5*1 allele predicts low dose-normalized tacrolimus blood concentrations in whites and South Asians.
Previously, we demonstrated that the dose-normalized tacrolimus blood concentration after renal transplantation was associated with a single nucleotide polymorphism (SNP) in the CYP3AP1 gene, probably through linkage with an SNP in the CYP3A5 gene. Individuals with at least one CYP3A5*1 allele synthesize CYP3A5 and CYP3A5*3/*3 homozygotes do not. We now present results with direct typing of the CYP3A5 genotype for this group of 180 kidney-only transplant recipients from a single center. South Asian and white patients with at least one CYP3A5*1 allele achieved twofold lower dose-normalized tacrolimus blood concentrations compared with CYP3A5*3/*3 homozygotes, confirming our previous findings for the CYP3AP1 SNP. There was a significant delay in achieving target blood concentrations in those with at least one CYP3A5*1 allele. Determination of the CYP3A5*1/*3 genotype could be used to predict the tacrolimus dose requirement and, given incomplete linkage, would be better than determination of the CYP3AP1 genotype.
Macphee
Iain A M
IA
Cellular and Molecular Medicine, Renal Medicine, St. George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK. imacphee@sghms.ac.uk
Fredericks
Salim
S
Mohamed
Maha
M
Moreton
Michelle
M
Carter
Nicholas D
ND
Johnston
Atholl
A
Goldberg
Lawrence
L
Holt
David W
DW
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D016559:Tacrolimus / Q000097:blood*; D044465:White People
D007166:Immunosuppressive Agents; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus