CYP4A11 T8590C polymorphism, salt-sensitive hypertension, and renal blood flow

Objective and methods A loss-of-function cytosine (C) for thymidine (T) transition at nucleotide 8590 of CYP4A11 has been associated with increased blood pressure in humans. We tested the hypothesis that CYP4A11 T8590C genotype is associated with salt sensitivity in the International Hypertensive Pathotype cohort. Results CYP4A11 T8590C genotype was associated with hypertension in whites. Among normotensive individuals, CYP4A11 T8590C genotype was associated with mean arterial pressure (MAP) during both high and low salt diets, such that there was no relationship between genotype and salt sensitivity of blood pressure. Among hypertensive individuals, CYP4A11 T8590C genotype did not associate with MAP during high salt intake, whereas MAP decreased with increasing number of C alleles during salt restriction. Consequently, among hypertensive individuals, change in MAP with salt restriction was greatest in individuals homozygous for the C allele (−10.9 ± 9.9, −11.1 ± 12.3, and −18.8 ± 12.0 mmHg in TT, CT, and CC groups, respectively, P = 0.02). In both normotensive and hypertensive individuals, individuals homozygous for the C allele exhibited an attenuated increase in renal blood flow during high salt. CYP4A11 genotype did not affect pressor responses to Angiotensin II in normotensive or hypertensive individuals. Conclusion The loss-of-function CYP4A11 8590C allele is associated with a diagnosis of hypertension and, in normotensive individuals, with higher blood pressure regardless of salt intake. Among hypertensive individuals, the C allele is associated with salt-sensitive blood pressure. Impaired renal vasodilation during high salt intake may contribute to salt sensitivity. Studies are needed to determine whether CYP4A11 T8590C genotype predicts responses to medications that affect sodium homeostasis in hypertensive individuals.