From INSERM U358, Hôpital Saint-Louis (E.B., N.C., I.F., F.S.), and
INSERM U36, Collège de France (P.M., K.C., X.J., P.C., L.P.), Paris,
France.
Correspondence to Florent Soubrier, INSERM U358, Hôpital Saint-Louis, 1, Ave Claude Vellefaux, 75475 Paris, cedex 10, France. E-mail Soubrier{at}inserm.chu-stlouis.fr
Abstract—Anomalies in either of the
tightly linked genes encoding the enzymes CYP11B1 (11ß-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.
© 1998 American Heart Association, Inc.
Scientific Contributions
Structural Analysis and Evaluation of the Aldosterone Synthase Gene in Hypertension
Key Words: aldosterone synthase • steroid 11ß-hydroxylase • biallelic polymorphism • microsatellite marker • association study • linkage study
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