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The prevalence of CYP2C9, 2J2, and soluble epoxide hydrolase (SEH) polymorphisms in African‐Americans (AA) on hemodialysis (HD)
Author(s) -
Dreisbach A. W.,
Japa S.,
Sigel A.,
Parenti M. B.,
Hess A. E.,
Srinnouanprachanh S.,
Farin F. M.,
Rettie A.E.,
Lertora J. J.
Publication year - 2005
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.2004.12.108
Subject(s) - medicine , allele , gastroenterology , epoxide hydrolase 2 , population , endocrinology , hemodialysis , cyp2c9 , biology , metabolism , genetics , cytochrome p450 , gene , enzyme , biochemistry , environmental health
Background CYP2C9, CYP2J2, and sEH have been shown to be involved in the formation and metabolism of vasoactive epoxides of the epoxygenase pathway which have been proposed to play a role in the pathogenesis of hypertension and progression of renal failure. The AA population with endstage renal disease (ESRD) on HD has a high prevalence of hypertension and may have altered prevalence of these polymorphisms Methods We studied the frequency of CYP2C9*8 and *11, sEH R287Q and anR403insertion, and CYP2J2*2‐*7 and the newly identified CYP2J2 polymorphisms R49S, L50L, V113M, N124S in 97 AA ESRD patients and 84 healthy AA to determine whether there is a significant difference in prevalence rates of these polymorphisms. The mean age of the ESRD patients was 53.3± 12.1 years (mean± sd) and the healthy AA was 38.6± 9.1 years. The ESRD patients and healthy subjects were 43.3% and 38.6 % female, respectively. The DNA was isolated from peripheral blood mononuclear cells and then genotyped for the variant alleles using TaqMan‐based allelic discrimination assays. Results The prevalence of the CYP2J2 variant alleles with the exception of CYP2J2*7 (see Table) ranged from 0 to 1.1% in the healthy and ESRD populations. Additional results are shown in the table below. Conclusions There was no significant difference in prevalence rates of the CYP2C9, CYP2J2, and sEH alleles in AA with ESRD compared with the healthy AA population. This is similar to the results we previously reported for CYP2C9*2–5 and CYP2C8*2‐*3. Clinical Pharmacology & Therapeutics (2005) 77 , P57–P57; doi: 10.1016/j.clpt.2004.12.108Prevalence of Epoxygenase SNPs In AA on HD Allele ESRD (%) N = 97 Healthy (%) N = 101 P Chi‐SquareCYP2C9*8 4.6 3.0 NS CYP2C9*11 2.1 1.0 NS sEH R287Q 10.8 8.0 NS sEH R403ins 0 2.0 NS CYP212*7 8.5 11.1 NS