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A novel functional genetic variant of CYP2J2 in a Korean population
Author(s) -
Ryu J.,
Jung H.,
Liu K.,
Lee S.,
Cha I.,
Shin J.
Publication year - 2004
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2003.11.360
Subject(s) - single nucleotide polymorphism , biology , population , allele , genetics , gene , genotype , medicine , environmental health
CYP2J2 is abundant in human heart and involves in the metabolism of arachidonic acid to eicosanoids that possess potent vasodilatory, antiinflammatory and cardioprotective properties. A number of allelic variants in CYP2J2 gene have been known to affect catalytic activity, including CYP2J2*2, *3, *4, *5, *6 and *7 in Caucasians. In the present study, genetic polymorphisms in CYP2J2 were screened by direct sequencing of genomic DNA from 96 healthy Korean subjects. There were twelve SNPs including three in 3′ UTR, three in introns, one in promoter and five SNPs in coding regions. CYP2J2*2, *3, *4, *5, and *6 were not found in the Korean population and CYP2J2*7 was observed with the allelic frequency of 5.17%. Two novel non‐synonymous SNPs (G18859A/Gly312Arg in exon 6 and C21685T/Pro351Leu in exon 7) were identified in a Korean population. To investigate the effects of the two SNPs on enzymatic activity, wild‐type and mutant‐type CYP2J2 proteins were produced in Sf9 insect cells using baculoviral expression system. CYP2J2 activity in baculosome was assessed with astemizole as a substrate for CYP2J2 using LC/MS/MS. G18859A variant caused lower catalytic activity of astemizole demethylation than wild‐type enzyme, and C21685T variant didn't influence on the enzyme activity. The allelic frequency of G18859A variant was 0.71% in 96 Korean subjects. Ethnic difference of allelic frequency and clinical relevance of this SNP are under our investigations. Clinical Pharmacology & Therapeutics (2004) 75 , P94–P94; doi: 10.1016/j.clpt.2003.11.360