HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

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.
AuthorsChristian L Lino Cardenas, Nicolas Renault, Amaury Farce, Christelle Cauffiez, Delphine Allorge, Jean-Marc Lo-Guidice, Michel Lhermitte, Philippe Chavatte, Franck Broly, Dany Chevalier
JournalGene (Gene) Vol. 487 Issue 1 Pg. 10-20 (Nov 01 2011) ISSN: 1879-0038 [Electronic] Netherlands
PMID21820496 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 Elsevier B.V. All rights reserved.
Chemical References
  • Fatty Acids
  • Cytochrome P-450 Enzyme System
  • CYP4A11 protein, human
  • CYP4A22 protein, human
  • Cytochrome P-450 CYP4A
Topics
  • Amino Acid Sequence
  • Binding Sites (genetics)
  • Biocatalysis
  • Computational Biology (methods)
  • Cytochrome P-450 CYP4A
  • Cytochrome P-450 Enzyme System (chemistry, genetics, metabolism)
  • Databases, Genetic
  • Fatty Acids (metabolism)
  • France
  • Gene Frequency
  • Genotype
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation, Missense
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide
  • Polymorphism, Single-Stranded Conformational
  • Protein Binding
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: