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Identification and functional studies of human CYP26A1 Single Nucleotide Polymorphisms (SNPs) in racially diverse populations
Author(s) -
Lee SuJun,
Coulter Sherry,
Jetten Anton M,
Goldstein Joyce A
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a264-b
Subject(s) - retinoic acid , biology , single nucleotide polymorphism , tretinoin , microbiology and biotechnology , retinoic acid inducible orphan g protein coupled receptor , retinoic acid receptor , phenotype , genetics , genotype , gene
Retinoic acid is a critical regulator of gene expression during embryonic development and in the maintenance of adult epithelial tissues. Genetic polymorphisms of CYP26A1 may cause inter‐individual variations in the metabolism of retinoic acid, resulting in different signaling in the development. A number of Single Nucleotide Polymorphisms (SNPs) were identified in CYP26A1 in 92 racially diverse individuals (24 Caucasians, 24 African‐Americans, 24 Asians and 20 individuals of unknown racial origin). Three SNPs produced coding changes: R173S, F186L and C358R. cDNA constructs for wild‐type and coding SNPs of CYP26A1 were prepared in pcDNA3.1 expression vector containing a FLAG tag at the C‐terminal end which was used to quantitate the proteins when expressed in Cos‐1 cells. CYP26A1 metabolizes all‐trans‐retinoic acid to 4‐oxo‐retinoic acid, 4‐OH‐retinoic acid and 18‐OH‐retinoic acid as well as water soluble metabolites. There were no metabolites of retinoic acid in cells transfected with pcDNA3.1 expression vector alone. When expressed in Cos‐1 cells, CYP26A1 F186L and CYP26A1 C358R exhibited a significant decrease in metabolism (50–70%) compared to that of wild‐type. CYP26A1 F186L and CYP26A1 C358R are predicted to be defective in retinoic acid metabolism in vivo. This in vitro characterization would be helpful to understand genotype/phenotype relationship in the future clinical study. This research was supported by the intramural division of the NIEHS.