title: Genetic polymorphism of CYP4A11 and CYP4A22 genes and in silico insights from comparative 3D modelling in a French population.
abstract: The CYP4A subfamily is known to ω-hydroxylate the endogenous arachidonic acid into 20-hydroxyeicosatetranoic acid, which has renovascular and tubular functions. The aim of this work was to report a comprehensive investigation of the CYP4A11 and CYP4A22 genetic polymorphisms in a French population. Using PCR-SSCP and sequencing strategies, a total of 26 sequence variations were identified comprising 3 missense mutations for CYP4A11 (Ser404Phe, Phe434Ser and Arg505His) and 7 missense mutations for CYP4A22 (Arg126Trp, Gly130Ser, Asn152Tyr, Val185Phe, Cys231Arg, Leu428Pro and Leu509Phe). In comparison with SNPs reported in the database (dbSNP) of the National Center for Biotechnology information (NCBI), 6 and 3 novel polymorphisms were identified in CYP4A11 and CYP4A22, respectively. The potential impact of the amino acid substitutions on the structure and/or catalytic activity of the enzymes has been estimated by the construction and validation of the CYP4A 3D models. These results could be helpful for further investigations of the potential role of CYP4A variants in the genetic susceptibility to cardiovascular diseases in humans such as arterial hypertension.
authors.affiliation: Université Lille Nord de France, Faculté de Médecine de Lille, Lille Cedex, France. lacks22@hotmail.com
authors.forename: Christian L
authors.initials: CL
authors.lastname: Lino Cardenas
authors.forename: Nicolas
authors.initials: N
authors.lastname: Renault
authors.forename: Amaury
authors.initials: A
authors.lastname: Farce
authors.forename: Christelle
authors.initials: C
authors.lastname: Cauffiez
authors.forename: Delphine
authors.initials: D
authors.lastname: Allorge
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Lo-Guidice
authors.forename: Michel
authors.initials: M
authors.lastname: Lhermitte
authors.forename: Philippe
authors.initials: P
authors.lastname: Chavatte
authors.forename: Franck
authors.initials: F
authors.lastname: Broly
authors.forename: Dany
authors.initials: D
authors.lastname: Chevalier
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D055162:Biocatalysis; D019295:Computational Biology / Q000379:methods*; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D030541:Databases, Genetic; D005227:Fatty Acids / Q000378:metabolism; D005602:France; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
chemical_list: D005227:Fatty Acids; D003577:Cytochrome P-450 Enzyme System; C465478:CYP4A11 protein, human; C471051:CYP4A22 protein, human; D042926:Cytochrome P-450 CYP4A