title: Association of the T8590C polymorphism of CYP4A11 with hypertension in the MONICA Augsburg echocardiographic substudy.
abstract: Genetic variants of the arachidonic acid monooxygenase CYP4A11 result in decreased synthesis of 20-hydroxyeicostatetraenoic acid and experimental hypertension. Moreover, in humans, the T8590C polymorphism of CYP4A11 displayed association with arterial hypertension. The aim of the present study was to further investigate this association in a large population-based sample. Therefore, the participants of the echocardiographic substudy of the third MONICA (MONitoring trends and determinants In CArdiovascular disease) survey (n=1397) were studied by standardized anthropometric, echocardiographic, and biochemical measurements as well as genotyping for CYP4A11 T8590C allele status. Individuals with the CC genotype have higher systolic (CC 141.4+/-3.17 mm Hg versus CT 134.2+/-0.97 mm Hg and TT 134.3+/-0.53 mm Hg; P=0.03) and diastolic blood pressure levels (CC 85.4+/-2.06 mm Hg versus CT 80.3+/-0.63 mm Hg and TT 80.7+/-0.34 mm Hg; P=0.02). Accordingly, the odds ratio (adjusted for age, body mass index, and gender) of the CC genotype versus the CT and TT genotypes for hypertension was 3.31 (95% confidence interval [CI]), 1.38 to 7.96; P=0.016) in the entire study population, with similar trends in men (4.30 [95% CI, 1.08 to 17.15]) and women (2.93 [95% CI, 0.88 to 9.84]). Consistent with the renal effects of the gene, no blood pressure-independent association between the T8590C polymorphism and echocardiographic parameters of left ventricular function and geometry was found. In conclusion, our data strengthen the association between the T8590C polymorphism of CYP4A11 and hypertension and suggest a recessive mode of inheritance. In contrast, we found no blood pressure-independent modulatory effect of CYP4A11 T8590C on cardiac size, structure, and function.
authors.affiliation: Medizinische Klinik II, Universitätsklinik Schleswig-Holstein, Campus Lübeck, D-23538 Lübeck, Germany.
authors.forename: Bjoern
authors.initials: B
authors.lastname: Mayer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Lieb
authors.forename: Anika
authors.initials: A
authors.lastname: Götz
authors.forename: Inke R
authors.initials: IR
authors.lastname: König
authors.forename: Zouhair
authors.initials: Z
authors.lastname: Aherrahrou
authors.forename: Annett
authors.initials: A
authors.lastname: Thiemig
authors.forename: Stephan
authors.initials: S
authors.lastname: Holmer
authors.forename: Christian
authors.initials: C
authors.lastname: Hengstenberg
authors.forename: Angela
authors.initials: A
authors.lastname: Doering
authors.forename: Hannelore
authors.initials: H
authors.lastname: Loewel
authors.forename: Hans-Werner
authors.initials: HW
authors.lastname: Hense
authors.forename: Heribert
authors.initials: H
authors.lastname: Schunkert
authors.forename: Jeanette
authors.initials: J
authors.lastname: Erdmann
mesh_terms: D000328:Adult; D000368:Aged; D001794:Blood Pressure; D003404:Creatinine / Q000097:blood; D003545:Cysteine; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004452:Echocardiography; D005260:Female; D006352:Heart Ventricles / Q000000981:diagnostic imaging; D006801:Humans; D006973:Hypertension / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013912:Threonine
chemical_list: D013912:Threonine; D003577:Cytochrome P-450 Enzyme System; D003404:Creatinine; C465478:CYP4A11 protein, human; D042926:Cytochrome P-450 CYP4A; D003545:Cysteine