title: Identification by single-strand conformational polymorphism analysis of known and new mutations of the CYP3A5 gene in a French population.
abstract: The cytochrome P450 3A5 (CYP3A5) has been shown to be highly involved in the metabolism of many therapeutic agents. To date, several polymorphisms affecting the CYP3A5 gene have been identified but few studies have shown a complete description of the variability of the CYP3A5 in the French population. Therefore, the extent of CYP3A5 genetic polymorphism was investigated in a French population of 114 patients. The screening of the coding region with their intron-exon boundaries and the proximal flanking regions was performed using a PCR-SSCP strategy. Eighteen polymorphisms were identified, including four new mutations. They correspond to -19 T>C upstream of the exon 1, 7360 T>C in intron 4, 12991 T>C in intron 5 and 29788 delG in exon 12. We also identified 13 alleles including six new alleles. As expected, the most frequent allelic variant is CYP3A5*3, with a frequency of 87% of all alleles. These data confirmed that CYP3A5 gene is highly polymorphic. Furthermore, it will be now interesting to evaluate the impact of this polymorphism on the pharmacokinetic parameters of different drugs.
authors.affiliation: FRE-CNRS 2737, Faculté de Pharmacie de Marseille, 27 Boulevard Jean Moulin, 13385 Marseille cedex 5, France. sylvie_quaranta@hotmail.com
authors.forename: Sylvie
authors.initials: S
authors.lastname: Quaranta
authors.forename: Dany
authors.initials: D
authors.lastname: Chevalier
authors.forename: Véronique
authors.initials: V
authors.lastname: Bourgarel-Rey
authors.forename: Delphine
authors.initials: D
authors.lastname: Allorge
authors.forename: Caroline
authors.initials: C
authors.lastname: Solas
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Lo-Guidice
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Sampol-Manos
authors.forename: Henri
authors.initials: H
authors.lastname: Vacher-Coponat
authors.forename: Valérie
authors.initials: V
authors.lastname: Moal
authors.forename: Franck
authors.initials: F
authors.lastname: Broly
authors.forename: Michel
authors.initials: M
authors.lastname: Lhermitte
authors.forename: Bruno
authors.initials: B
authors.lastname: Lacarelle
mesh_terms: D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000145:classification / Q000235:genetics*; D005602:France; D005787:Gene Frequency; D005828:Genetics, Population / Q000379:methods*; D006801:Humans; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: D003577:Cytochrome P-450 Enzyme System; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A