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PI‐30
Author(s) -
Kroetz D. L.,
Yu Z.,
Langaee T. Y.,
Johnson J. A.
Publication year - 2006
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.2005.12.051
Subject(s) - epoxide hydrolase 2 , medicine , essential hypertension , endocrinology , genotype , allele , blood pressure , allele frequency , minor allele frequency , biology , genetics , enzyme , biochemistry , gene
BACKGROUND/AIMS CYP2J2 catalyzes the formation of epoxyeicosatrienoic acids (EETs) with antihypertensive properties. The effects of the EETs are attenuated through hydrolysis by soluble epoxide hydrolase (sEH encoded by EPHX2 ). This study examined whether genetic variants of CYP2J2 and EPHX2 with decreased function/expression in vitro are associated with hypertension (HTN). METHODS Hypertensive (HT; n=199) and normotensive (NT; n=125) African Americans (AA) and HT (n=187) and NT (n=175) Caucasians (CA) between 35–65 years of age were studied. NT had BP< 140/90 mmHg and no primary family history of HTN. The following variants were genotyped by pyrosequencing: in AA the 372C>T (Arg103Cys) and 925G>A (Arg287Gln) variants of EPHX2 , and in AA and CA the CYP2J2 *7 promoter allele. Minor allele frequencies (MAFs) were compared between NT and HT using a Chi‐square test and differences in blood pressure between genotype groups was compared with a t ‐test. RESULTS The MAF (see Table) for the EPHX2 and CYP2J2 variants were similar in NT and HT. DBP and SBP were not associated with the EPHX2 or CYP2J2 genotypes or EPHX2 diplotypes.EPHX2 372C>T EPHX2 925G>A CYP2J2*7NT AA 11% 9.2% 12%HT AA 9.6% 8.7% 12%NT CA8.6%HT CA8.8%CONCLUSIONS Functionally significant genetic variants of CYP2J2 and EPHX2 are not associated with HTN in AA and CA. The importance of these variants in the progression of cardiac endpoints associated with HTN is being investigated. Clinical Pharmacology & Therapeutics (2005) 79 , P15–P15; doi: 10.1016/j.clpt.2005.12.051