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.