The T8590C Polymorphism of CYP4A11 and 20-Hydroxyeicosatetraenoic Acid in Essential Hypertension.

The T8590C Polymorphism of CYP4A11 and 20-Hydroxyeicosatetraenoic Acid in Essential Hypertension. Research Abstract Details 

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The T8590C Polymorphism of CYP4A11 and 20-Hydroxyeicosatetraenoic Acid in Essential Hypertension. Abstract Text:

Cheryl L Laffer,James V Gainer,Michael R Waterman,Jorge H Capdevila,Michal Laniado-Schwartzman,Alberto Nasjletti,Nancy J Brown,Fernando Elijovich,

A role for a deficit in transport actions of 20-hydroxyeicosatetraenoic acid (20-HETE) in hypertension is supported by the following: (1) diminished renal 20-HETE in Dahl-S rats; (2) altered salt- and furosemide-induced 20-HETE responses in salt-sensitive hypertensive subjects; and (3) increased population risk for hypertension in C allele carriers of the T8590C polymorphism of CYP4A11, which encodes an enzyme with reduced catalytic activity. We determined T8590C genotypes in 32 hypertensive subjects, 25 of whom were phenotyped for salt sensitivity of blood pressure and insulin sensitivity. Urine 20-HETE was lowest in insulin-resistant, salt-sensitive subjects (F=5.56; P<0.02). Genotypes were 13 TT, 2 CC, and 17 CT. C allele frequency was 32.8% (blacks: 38.9%; whites: 25.0%). C carriers (CC+CT) and TT subjects were similarly distributed among salt- and insulin-sensitivity phenotypes. C carriers had higher diastolic blood pressures and aldosterone:renin and waist:hip ratios but lower furosemide-induced fractional excretions of Na and K than TT. The T8590C genotype did not relate to sodium balance or pressure natriuresis. However, C carriers, compared with TT, had diminished 20-HETE responses to salt loading after adjustment for serum insulin concentration and resetting of the negative relationship between serum insulin and urine 20-HETE to a 1-mug/h lower level of 20-HETE. The effect of C was insulin independent and equipotent to 18 muU/mL of insulin (Delta20-HETE= 2.84-0.054xinsulin-0.98xC; r(2)=0.53; F=11.1; P<0.001). Hence, genetic (T8590C) and environmental (insulin) factors impair 20-HETE responses to salt in human hypertension. We propose that genotype analyses with sufficient homozygous CC will establish definitive relationships among 20-HETE, salt sensitivity of blood pressure, and insulin resistance.

The T8590C Polymorphism of CYP4A11 and 20-Hydroxyeicosatetraenoic Acid in Essential Hypertension. Publishing Authors By Initials

CL Laffer,JV Gainer,MR Waterman,JH Capdevila,M Laniado-Schwartzman,A Nasjletti,NJ Brown,F Elijovich,

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The T8590C Polymorphism of CYP4A11 and 20-Hydroxyeicosatetraenoic Acid in Essential Hypertension. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Hypertension

VOLUME: 51

Page Numbers: 767-72

Journal Abbreviation: Hypertension

ISSN: 1524-4563

DAY: 28

MONTH: 01

YEAR: 2008

The T8590C Polymorphism of CYP4A11 and 20-Hydroxyeicosatetraenoic Acid in Essential Hypertension. Information

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LANGUAGE: eng

NlmUniqueID: 7906255

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AFFILIATION: Texas A&M Health Science Center College of Medicine, Scott and White-Hypertension/Nephrology, 2401 S 31st St, Temple, TX 76508. claffer@swmail.sw.org.

Country: United States

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MEDLINETA: Hypertension

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