Genetic variation in aldosterone synthase predicts plasma glucose levels
Journal
Proceedings of the National Academy of Sciences of the United States of America
Journal Volume
98
Journal Issue
23
Pages
13219-13224
Date Issued
2001
Author(s)
Ranade K.
Risch N.
Olivier M.
Pei D.
Hsiao C.-F.
Ho L.-T.
Jorgenson E.
Pesich R.
Chen Y.-D.I.
Dzau V.
Lin A.
Olshen R.A.
Curb D.
Cox D.R.
Botstein D.
Abstract
The mineralocorticoid hormone, aldosterone, is known to play a role in sodium homeostasis. We serendipitously found, however, highly significant association between single-nucleotide poly-morphisms in the aldosterone synthase gene and plasma glucose levels in a large population of Chinese and Japanese origin. Two poly-morphisms-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 poly-morphisms, 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.
SDGs
Other Subjects
aldosterone synthase; amino acid; arginine; glucose; lysine; sodium; adult; amino acid substitution; article; Chinese; diabetes mellitus; female; gene linkage disequilibrium; genetic variability; glucose blood level; glucose metabolism; homozygosity; human; intron; Japan; major clinical study; male; priority journal; promoter region; single nucleotide polymorphism; Adult; Aldosterone Synthase; Base Sequence; Blood Glucose; Diabetes Mellitus; DNA Primers; Female; Genotype; Glucose Tolerance Test; Humans; Insulin; Male; Middle Aged; Variation (Genetics)
Type
journal article