title: A search for new CYP3A4 variants as determinants of tacrolimus dose requirements in renal-transplanted patients.
abstract: The CYP3A5*3 and CYP3A4*1B alleles have been related with tacrolimus (Tac) dose requirements. The rare CYP3A4*22 variant has also been associated with a significantly lower Tac dose. We genotyped the three single-nucleotide polymorphisms in 206 kidney-transplanted patients who received Tac as the primary immunosuppressor. CYP3A5*1 and CYP3A4*1B allele carriers received a significantly higher Tac dose (P<0.01) compared with wild-type homozygotes. We did not find significant differences between the CYP3A4*22 genotypes, either nominally or according to the CYP3A5 genotype (expressers vs. nonexpressers). Sequencing of CYP3A4 coding exons in a total of 15 patients revealed only one nonreported missense change (p.P227>T) in one patient. We concluded that CYP3A5*3 and CYP3A4*1B were the main determinants of the Tac dose-adjusted blood concentration in our cohort of renal-transplanted patients.
authors.affiliation: Molecular Genetics-Laboratory of Medicine, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Tavira
authors.forename: Eliecer
authors.initials: E
authors.lastname: Coto
authors.forename: Carmen
authors.initials: C
authors.lastname: Diaz-Corte
authors.forename: Victoria
authors.initials: V
authors.lastname: Alvarez
authors.forename: Carlos
authors.initials: C
authors.lastname: López-Larrea
authors.forename: Francisco
authors.initials: F
authors.lastname: Ortega
mesh_terms: D000328:Adult; D000368:Aged; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D006084:Graft Rejection; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000097:blood; D016030:Kidney Transplantation; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016559:Tacrolimus / Q000008:administration & dosage* / Q000097:blood
chemical_list: D007166:Immunosuppressive Agents; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D016559:Tacrolimus