Anomalies in either of the tightly linked genes encoding the
enzymes CYP11B1 (11beta-hydroxylase) or
CYP11B2 (
aldosterone synthase) can lead to important changes in arterial pressure and are responsible for several monogenically inherited forms of
hypertension. Mutations in these genes or their regulatory regions could thus contribute to genetic variation in susceptibility to
essential hypertension. To test this hypothesis, we performed 2 complementary studies of the
CYP11B1/
CYP11B2 locus in
essential hypertension. After characterizing
a DNA contig containing the
CYP11B1 gene and mapping the gene in the Centre d'Etudes du Polymorphisme Humain reference panel of families, we performed a linkage study with 292 hypertensive sibling pairs and a highly informative microsatellite marker near
CYP11B1. We also analyzed the association of 2 frequent biallelic polymorphisms of the
CYP11B2 gene, 1 in the promoter at position -344 (-344C/T) and the other, a common gene conversion in intron 2, with
hypertension in 380 hypertensive patients and 293 normotensive individuals. Statistical analyses did not show significant linkage of the
CYP11B1 microsatellite marker to
hypertension. No positive association with
hypertension was found with the gene conversion in intron 2, but a positive association with
hypertension was found with the -344T allele. The hypertensive and normotensive samples differed significantly in both genotype (P=0.023) and allele frequencies (P=0.010). Our data suggest a modest contribution of the
CYP11B2 gene to
essential hypertension.