Clinical and genetic correlates of serum aldosterone in the community: the Framingham Heart Study.
BACKGROUND
We investigated the environmental and genetic sources of interindividual variability in serum aldosterone level in a large, community-based sample.


METHODS
We examined the relation of serum aldosterone to vascular risk factors, urine sodium, and candidate single nucleotide polymorphisms in 2891 Framingham Offspring Study participants (53.2% women, mean age 59 years) using multivariable linear regression. Multivariable logistic regression was used to identify predictors of high (top quartile) and low (lowest quartile) serum aldosterone values. We estimated heritability of serum aldosterone via variance-component methods and evaluated linkage via a 10-cM-density genome scan.


RESULTS
Clinical variables related to higher serum aldosterone level included female sex, diuretic treatment, and a higher total/high density lipoprotein cholesterol ratio. A high urinary sodium excretion, postmenopausal status (without hormone replacement therapy), increased pulse pressure, and prevalent cardiovascular disease were related to lower serum aldosterone values. Urinary sodium was the strongest correlate of serum aldosterone (R2= 10%). Serum aldosterone levels did not differ by genotype in the aldosterone synthase (CYP11B2c.1-344C>T) and the mineralocorticoid receptor (NR3C2c.754A>G) genes. The estimated heritability of serum aldosterone was 0.10. No chromosomal region attained a log-of-the-odds score >1 in multipoint linkage analysis.


CONCLUSIONS
We observed a complex relation between serum aldosterone and vascular risk factors. The genetic contribution to serum aldosterone level was modest.
Kathiresan
Sekar
S
National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts 01702-5827, USA.
Larson
Martin G
MG
Benjamin
Emelia J
EJ
Corey
Diane
D
Murabito
Joanne M
JM
Fox
Caroline S
CS
Wilson
Peter W F
PW
Rifai
Nader
N
Meigs
James B
JB
Ricken
Gesa
G
Lifton
Richard P
RP
Levy
Daniel
D
Vasan
Ramachandran S
RS
D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood*; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D018161:Receptors, Mineralocorticoid / Q000235:genetics; D012307:Risk Factors; D012964:Sodium / Q000652:urine
D018161:Receptors, Mineralocorticoid; D000450:Aldosterone; D012964:Sodium; D019405:Cytochrome P-450 CYP11B2