Genetic variation in aldosterone synthase predicts plasma glucose levels.
The mineralocorticoid hormone, aldosterone, is known to play a role in sodium homeostasis. We serendipitously found, however, highly significant association between single-nucleotide polymorphisms in the aldosterone synthase gene and plasma glucose levels in a large population of Chinese and Japanese origin. Two polymorphisms--one in the putative promoter (T-344C) and another resulting in a lysine/arginine substitution at amino acid 173, which are in complete linkage disequilibrium in this population--were associated with fasting plasma glucose levels (P = 0.000017) and those 60 (P = 0.017) and 120 (P = 0.0019) min after an oral glucose challenge. A C/T variant in intron 1, between these polymorphisms, was not associated with glucose levels. Arg-173 and -344C homozygotes were most likely to be diabetic [odds ratio 2.51; 95% confidence interval (C.I.) 1.39-3.92; P = 0.0015] and have impaired fasting glucose levels (odds ratio 3.53; 95% C.I. 2.02-5.5; P = 0.0000036). These results suggest a new role for aldosterone in glucose homeostasis.
Ranade
K
K
Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305-5120, USA. koustubh.ranade@bms.com
Wu
K D
KD
Risch
N
N
Olivier
M
M
Pei
D
D
Hsiao
C F
CF
Chuang
L M
LM
Ho
L T
LT
Jorgenson
E
E
Pesich
R
R
Chen
Y D
YD
Dzau
V
V
Lin
A
A
Olshen
R A
RA
Curb
D
D
Cox
D R
DR
Botstein
D
D
D000328:Adult; D001483:Base Sequence; D001786:Blood Glucose / Q000032:analysis*; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics*; D017931:DNA Primers; D003920:Diabetes Mellitus / Q000097:blood / Q000201:enzymology / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged
D001786:Blood Glucose; D017931:DNA Primers; D007328:Insulin; D019405:Cytochrome P-450 CYP11B2