Genetic variation in aldosterone synthase predicts plasma glucose levels

The mineralocorticoid hormone, aldosterone, is known to play a role in sodi um homeostasis. We serendipitously found, however, highly significant assoc iation between sing le-nucleotide polymorphisms in the alosterone synthase gene and plasma glucose levels in a large population of Chinese and Japanes e origin, Two polymorphisms-one in the putative promoter (T-344C) and anoth er 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 intr on 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 impaire d 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.