Frequencies of CYP3A5*1/*3 variants in a Moroccan population and effect on tacrolimus daily dose requirements in renal transplant patients.
The cytochromes P450 are a superfamily of oxidative enzymes, which are implicated in the metabolism of a large number of endogenous substances as well as exogenous chemicals. The cytochrome P450 (CYP3A5) appears to play an important role in drug metabolism activity. The most frequent mutation in the CYP3A5 gene, affecting its activity, consists of a G6986A transition within intron 3. In this study, we determined the allelic frequency of CYP3A5*3 in a Moroccan population, consisting of 108 individuals including 10 renal transplant patients. About 8.33% (9/108) of the subjects were homozygous wild-type (CYP3A5*1/*1), 37.04% (40/108) were heterozygous (CYP3A5*1/*3), and 54.63% (59/108) were homozygous (CYP3A5*3/*3). Therefore, CYP3A5*3 variant was the most frequent allele detected at 73.15%. In the second part of this work, we assessed the influence of the CYP3A5 polymorphism on tacrolimus doses required for 10 renal transplant patients who are receiving tacrolimus as immunosuppressive therapy. Our results showed that, during the first 3 months after kidney transplantation, the tacrolimus daily requirements for heterozygous patients (CYP3A5*3/*1) were higher compared with homozygous patients (CYP3A5*3/*3) (0.133 ± 0.026 vs. 0.21 ± 0.037 mg/kg/day). After the third month the difference was also observed, whereby the mean of tacrolimus daily requirements for patients with CYP3A5*3/*3 and CYP3A5*1/*3 was 0.053 ± 0.013 and 0.08 ± 0.014 mg/kg/day, respectively. This first study in Morocco provides genetic data related to the frequency of genetic polymorphisms of CYP3A5 and opens the perspective to develop other pharmacogenetic studies.
Centre de Génomique Humaine, Faculté de Médecine et de Pharmacie, Université Mohammed V Souissi, Rabat, Morocco. elmachad@hotmail.fr
Mustapha
M
Elmachad
Driss
D
Elkabbaj
Fatiha
F
Elkerch
Fatima Zahra
FZ
Laarabi
Amina
A
Barkat
Zouhir
Z
Oualim
Abdelaziz
A
Sefiani
D000328:Adult; D044383:Black People / Q000235:genetics*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005787:Gene Frequency; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000378:metabolism; D007231:Infant, Newborn; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009018:Morocco; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D016559:Tacrolimus / Q000008:administration & dosage* / Q000378:metabolism; D055815:Young Adult
D007166:Immunosuppressive Agents; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus