Y. Jarrar,1 S. Cho,1 J. Park,1 M. Lee,1 W. Kim,1 D. Kim,1 S. Lee,1 J. Shin2; 1Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Korea, Republic of, 2Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine; Department of Clinical Pharmacology, Inje University Busan Paik Hospital, Busan, Korea, Republic of

BACKGROUND: Cytochrome 4V2 is a newly identified P450 with an oxidation activity toward saturated fatty acids, such as lauric and palmitic acids. Studies reported that CYP4V2 genetic variants were strongly associated with deep venous thrombosis and Bietti Crystalline Corneoretinal Dystrophy. The aim of the present study was to investigate the genetic variants of CYP4V2 gene and to find the functional change of the non-synonymous genetic variants among healthy Korean population.
METHODS: The data of the genetic variants on CYP4V2 gene were obtained from Next Generation Sequencing of the CYP4V2 and confirmed them by direct DNA sequencing of CYP4V2.
RESULTS: The results showed that 9 CYP4V2 variants were novel among Koreans; 3 were non-synonymous, 2 synonymous and 4 intron variants. Therefore, the 3 novel non-synonymous and 3 previously reported non-synonymous variants were cloned, in addition to the wild-type CYP4V2, in pcDNA/PDEST40 vector and expressed in freestyle 293T cells for in vitro functional studies. The results showed that CYP4V2 H331P and G410C, respectively, had a significant (P<0.001) decreased oxidation activity toward lauric acid using 2 different substrate concentrations, 125 and 250 ┬ÁM, in comparison to the wild type CYP4V2. The decrease in the lauric acid activities by H331P and G410C substitution was correlated with the decreased protein expression of variant CYP4V2 comparing to the wild type, as shown by western blot analysis.
CONCLUSION: The present study identified the CYP4V2 genetic variants with molecular functionality. The data of the present study will increase our understanding of CYP4V2 genetic variant associated diseases and inter-individual variations in fatty acid oxidation.