Michael Waterman
Faculty Member
Last active: 2/12/2015

Association of a CYP4A11 variant and blood pressure in black men.

Gainer JV, Lipkowitz MS, Yu C, Waterman MR, Dawson EP, Capdevila JH, Brown NJ, AASK Study Group
J Am Soc Nephrol. 2008 19 (8): 1606-12

PMID: 18385420 · PMCID: PMC2488260 · DOI:10.1681/ASN.2008010063

CYP4A11 arachidonic acid monooxygenase oxidizes endogenous arachidonic acid to 20-hydroxyeicosatetraenoic acid, a renal vasoconstrictor and natriuretic. Cyp4a deficiency causes hypertension in male mice, and a loss-of-function variant (T8590C) of CYP4A11 is associated with hypertension in white individuals. Hypertension and hypertensive renal disease are more common among black than white individuals, but the relationship between genetic variation at CYP4A11 and hypertension in black individuals is not known. This study tested the hypothesis that the CYP4A11 T8590C polymorphism is associated with higher BP or clinical outcomes in 732 black Americans with hypertensive renal disease participating in the African American Study of Kidney Disease (AASK). Men with the 8590CC genotype had significantly higher systolic BP (CC 156.5 +/- 22.6 versus 148.4 +/- 24.3 mmHg in CT and TT combined; P = 0.04) and pulse pressure (P = 0.04) at baseline; this association was not observed among women. In addition, this genotype was associated with higher systolic and diastolic BP at 36-mo follow-up among those randomly assigned to the lower BP arm of the AASK. Among all participants (or men but not women) with proteinuria, the 8590CC genotype was associated with an increased cumulative incidence of ESRD or death, controlling for randomization and clinical characteristics. In summary, the CYP4A11 8590CC genotype is associated with increased BP in black men with hypertensive nephrosclerosis and is associated with adverse clinical outcomes in those with baseline proteinuria. These data support a role for renal monooxygenases and 20-hydroxyeicosatetraenoic acid in the regulation of BP and renal function in men.

MeSH Terms (15)

Adult African Americans Antihypertensive Agents Blood Pressure Cytochrome P-450 CYP4A Cytochrome P-450 Enzyme System Disease Progression Genetic Variation Genotype Humans Hypertension Male Middle Aged Nephrosclerosis Sex Characteristics

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