Aldosterone synthase gene (CYP11B2) C-344T polymorphism in Caucasians from the Berlin Salt-Sensitivity Trial (BeSST).
OBJECTIVE
Aldosterone synthase (CYP11B2) is a key enzyme in the biosynthesis of aldosterone. Recently, the T allele of a polymorphism in the 5'-flanking region of the CYP11B2 gene (C-344T) has been reported to be more frequent in hypertensives than in normotensives, and has also been associated with increased plasma aldosterone levels. We therefore hypothesized that this variant may be related to increased blood-pressure response to dietary salt intake.


METHODS
We genotyped 1 63 young normotensive men recruited within the framework of the Berlin Salt-Sensitivity Trial (BeSST) for the CYP11B2 C-344T polymorphism. Subjects were characterized for family history of hypertension, plasma parameters of the renin-angiotensin-aldosterone system and blood-pressure response to a high (220 mmol/day) and low (20 mmol/day) salt diet


RESULTS
The frequency of the -344T allele (0.45) was similar to that reported previously and genotype distribution was in Hardy-Weinberg equilibrium (CC, n = 55; CT, n = 71; TT, n = 37). There was a trend towards a higher frequency of the T allele in subjects with a positive family history of hypertension (0.48 versus 0.42), but the C-344T genotype was not related to blood pressure under either diet Furthermore, when subjects were classified into salt-sensitive and salt-resistant groups, allelic distribution did not differ between the two groups (qT = 0.43 versus qT = 0.45). While renin activity and plasma aldosterone levels were not related to genotype, plasma angiotensinogen was significantly higher in T-allele carriers under both the high (P = 0.02) and low (P = 0.008) salt diet.


CONCLUSIONS
Our findings do not support the hypothesis that the C-344T polymorphism of the CYP11B2 gene is associated with salt sensitivity or increased activity of the renin-angiotensin system in young normotensive subjects. It is, therefore, unlikely that the C-344T polymorphism is a genetic marker for salt sensitivity in young normotensive Caucasian men.
Brand
E
E
Department of Internal Medicine, Universitätsklinkum Benjamin Franklin, Freie Universität Berlin, Germany.
Schorr
U
U
Ringel
J
J
Beige
J
J
Distler
A
A
Sharma
A M
AM
D000328:Adult; D000450:Aldosterone / Q000097:blood; D000483:Alleles; D000808:Angiotensinogen / Q000097:blood; D000886:Anthropometry; D001794:Blood Pressure / Q000187:drug effects*; D018592:Cross-Over Studies; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics*; D004039:Diet, Sodium-Restricted; D004351:Drug Resistance; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics* / Q000502:physiology; D012083:Renin / Q000097:blood; D016037:Single-Blind Method; D012965:Sodium Chloride / Q000008:administration & dosage* / Q000494:pharmacology; D044465:White People / Q000235:genetics*
D000808:Angiotensinogen; D012965:Sodium Chloride; D000450:Aldosterone; D019405:Cytochrome P-450 CYP11B2; D012083:Renin