Published online before print August 19, 2002, doi: 10.1161/01.HYP.0000032278.75806.68
(Hypertension. 2002;40:485.)
© 2002 American Heart Association, Inc.
Scientific Contributions |
Polymorphism in Soluble Epoxide Hydrolase and Blood Pressure in Spontaneously Hypertensive Rats
From the Institute of Molecular Medicine (M.F., C.A.H., B.W.N., P.A.D.) and Human Genetics Center (E.B.), University of Texas Health Sciences Center, Houston, Tex; and the Department of Entomology and Cancer Research Center, University of California at Davis (B.D.H., C.H.P.M.), Davis, Calif.
Correspondence to Peter A. Doris, PhD, Institute for Molecular Medicine, University of Texas Health Sciences Center, 2121 Holcombe Blvd, Houston TX, 77030. E-mail peter.a.doris{at}uth.tmc.edu
We measured soluble epoxide hydrolase (sEH) renal gene expression in prehypertensive (4 to 5 weeks old) spontaneously hypertensive rats of the Heidelberg SP substrain (SHR [Heid]) and when blood pressure levels entered the hypertensive plateau (17 to 18 weeks old) and compared expression with matched Wistar-Kyoto (WKY [Heid]) rats. Less expression of the gene encoding sEH (EPHX2) was observed in SHR (Heid) than in WKY (Heid). Analysis of sEH protein abundance showed a similar difference. However, no correlation between sEH abundance and blood pressure was observed in the F2 progeny of a parental strain cross. Measurement of protein abundance in SHR and WKY obtained from Charles River confirmed a recent report that abundance of sEH was greater in SHR (CRiv) than WKY (CRiv) strains. Polymorphisms were detected in EPHX2. Resequencing revealed that 2 alleles of EPHX2 exist in these 4 rat strains, differing by 4 single nucleotide polymorphisms, of which 3 produce nonsynonymous amino acid substitutions. The ancestral allele was shared by SHR (Heid) and WKY (CRiv), and the variant allele was shared by WKY (Heid) and SHR (CRiv). Activity of sEH was greater in animals carrying the variant allele. However, inheritance of this allele was not correlated with blood pressure in the F2 progeny of a cross between SHR (Heid) and WKY (Heid). These data indicate that sequence variation determining functional alterations in EPHX2 is not likely to contribute to blood pressure levels in SHR.
Key Words: hypertension, genetic • polymorphism • genetics • metabolism • rats, inbred SHR
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