title: Genetic variation in aldosterone synthase predicts plasma glucose levels.
abstract: 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.
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305-5120, USA. koustubh.ranade@bms.com
authors.forename: K
authors.initials: K
authors.lastname: Ranade
authors.forename: K D
authors.initials: KD
authors.lastname: Wu
authors.forename: N
authors.initials: N
authors.lastname: Risch
authors.forename: M
authors.initials: M
authors.lastname: Olivier
authors.forename: D
authors.initials: D
authors.lastname: Pei
authors.forename: C F
authors.initials: CF
authors.lastname: Hsiao
authors.forename: L M
authors.initials: LM
authors.lastname: Chuang
authors.forename: L T
authors.initials: LT
authors.lastname: Ho
authors.forename: E
authors.initials: E
authors.lastname: Jorgenson
authors.forename: R
authors.initials: R
authors.lastname: Pesich
authors.forename: Y D
authors.initials: YD
authors.lastname: Chen
authors.forename: V
authors.initials: V
authors.lastname: Dzau
authors.forename: A
authors.initials: A
authors.lastname: Lin
authors.forename: R A
authors.initials: RA
authors.lastname: Olshen
authors.forename: D
authors.initials: D
authors.lastname: Curb
authors.forename: D R
authors.initials: DR
authors.lastname: Cox
authors.forename: D
authors.initials: D
authors.lastname: Botstein
mesh_terms: 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
chemical_list: D001786:Blood Glucose; D017931:DNA Primers; D007328:Insulin; D019405:Cytochrome P-450 CYP11B2