Genetic determination of plasma aldosterone levels in essential hypertension.
The renin-angiotensin-aldosterone system plays an important role in large artery structure and blood pressure homeostasis. Among the genes coding for different components of this system, the aldosterone synthase (CYP11B2) gene could play an important role, but has been less investigated. We examined the role of two variations of the aldosterone synthase gene (CYP11B2), one located in the promoter of the gene, T-344C, the other in the 7th exon, the T4986C (Val/Ala), on plasma levels of renin and aldosterone, blood pressure, and arterial stiffness in subjects with essential hypertension. Subjects of European origin (n = 216) were examined during a 1-day hospitalization. Treatment, if any, was interrupted for at least 21 days before. Arterial stiffness was evaluated by measuring pulse wave velocity. Renin and aldosterone levels were evaluated by using a radioimmunoassay. The two polymorphisms were in complete linkage disequilibrium, as suggested by the presence of only three haplotypes in this population (T-344T4986, T-344C4986, and C-344T4986). The mean age and blood pressure values were similar in the different genotypes. Presence of the -344C allele was associated with elevated levels of plasma aldosterone: 90 +/- 8 pg/mL for TT (n = 67), 110 +/- 6 pg/mL for TC (n = 107), and 129 +/- 10 pg/mL for CC (n = 42) (test of codominant effect, P < .002 after adjustment for age and 24-h Na+ urine excretion). Pulse wave velocity was also increased in the -344C allele carriers: 11.3 +/- 0.4 m/sec, 12.7 +/- 0.3 m/sec, 12.0 +/- 0.5 m/sec in the TT, TC, and CC genotypes, respectively. No association was found between the T4986C polymorphism and the studied variables. In patients with essential hypertension, a variant on the promoter region of the aldosterone synthase gene is associated with significant differences in plasma aldosterone levels and arterial stiffness. These differences are not associated with variations in blood pressure levels.
INSERM U337, Broussais Hospital, Paris, France.
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D000367:Age Factors; D000450:Aldosterone / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001783:Blood Flow Velocity / Q000235:genetics / Q000502:physiology; D001794:Blood Pressure / Q000235:genetics / Q000502:physiology; D001827:Body Height / Q000235:genetics / Q000502:physiology; D001835:Body Weight / Q000235:genetics / Q000502:physiology; D016009:Chi-Square Distribution; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics; D003971:Diastole; D005787:Gene Frequency; D005820:Genetic Testing; D005838:Genotype; D006339:Heart Rate / Q000235:genetics / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D011110:Polymorphism, Genetic; D011674:Pulse; D012083:Renin / Q000097:blood; D012964:Sodium / Q000652:urine; D013599:Systole
D015415:Biomarkers; D000450:Aldosterone; D012964:Sodium; D019405:Cytochrome P-450 CYP11B2; D012083:Renin