title: First report of a genetic polymorphism of the cytochrome P450 3A43 (CYP3A43) gene: identification of a loss-of-function variant.
abstract: In the present study, we report the first investigation of polymorphisms in the human CYP3A43 gene. A screening for sequence variations in the 5'-flanking and protein coding regions of the CYP3A43 gene was performed by a Polymerase Chain Reaction - Single Strand Conformational Polymorphism (PCR-SSCP) strategy, using DNA samples from 48 unrelated French individuals. Three polymorphisms in the coding region were identified, comprising two nucleotide substitutions, one silent (c.1047C>T) and one missense mutation (c.1018C>G/P340A), and a frame shift mutation (c.74delA), leading to a premature stop codon and, presumably, to a severely truncated protein. In order to evaluate the extent of the frame shift mutation in a larger population, 352 individuals were further genotyped. Thirty-four samples (4.83%) were found to be heterozygous and one homozygous (0.14%) for the nucleotide deletion, which suggests that, although the potential significance of this polymorphism remains to be further evaluated, some individuals are deficient for CYP3A43 activity.
authors.affiliation: Equipe d'accueil 2679, Faculté de Médecine de Lille, Pôle Recherche, Lille, France. christelle.cauffiez@caramail.com
authors.forename: Christelle
authors.initials: C
authors.lastname: Cauffiez
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Lo-Guidice
authors.forename: Dany
authors.initials: D
authors.lastname: Chevalier
authors.forename: Delphine
authors.initials: D
authors.lastname: Allorge
authors.forename: Rima
authors.initials: R
authors.lastname: Hamdan
authors.forename: Michel
authors.initials: M
authors.lastname: Lhermitte
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Lafitte
authors.forename: Jean-Frédéric
authors.initials: JF
authors.lastname: Colombel
authors.forename: Christian
authors.initials: C
authors.lastname: Libersa
authors.forename: Franck
authors.initials: F
authors.lastname: Broly
mesh_terms: D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D004252:DNA Mutational Analysis; D006801:Humans; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; C422408:CYP3A43 protein, human