Ranade K.KWAN-DUN WURisch N.Olivier M.Pei D.Hsiao C.-F.LEE-MING CHUANGHo L.-T.Jorgenson E.Pesich R.Chen Y.-D.I.Dzau V.Lin A.Olshen R.A.Curb D.Cox D.R.Botstein D.2020-06-012020-06-0120010027-8424https://www.scopus.com/inward/record.uri?eid=2-s2.0-0035818572&doi=10.1073%2fpnas.221467098&partnerID=40&md5=9d987d18149bfd3da6a99ac4c0b384d5https://scholars.lib.ntu.edu.tw/handle/123456789/495827The 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]SDG3aldosterone 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)Genetic variation in aldosterone synthase predicts plasma glucose levelsjournal article10.1073/pnas.221467098116876122-s2.0-0035818572