First report of a genetic polymorphism of the cytochrome P450 3A43 (CYP3A43) gene: identification of a loss-of-function variant.
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.
Cauffiez
Christelle
C
Equipe d'accueil 2679, Faculté de Médecine de Lille, Pôle Recherche, Lille, France. christelle.cauffiez@caramail.com
Lo-Guidice
Jean-Marc
JM
Chevalier
Dany
D
Allorge
Delphine
D
Hamdan
Rima
R
Lhermitte
Michel
M
Lafitte
Jean-Jacques
JJ
Colombel
Jean-Frédéric
JF
Libersa
Christian
C
Broly
Franck
F
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
D001189:Aryl Hydrocarbon Hydroxylases; C422408:CYP3A43 protein, human