Genetic Variation in Aldosterone Synthase Predicts Plasma Glucose Levels

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 98; no. 23; pp. 13219 - 13224
• Main Authors: Ranade, Koustubh, Wu, Kwan Dun, Risch, Neil, Olivier, Michael, Pei, Dee, Hsiao, Chin-Fu, Chuang, Lee-Ming, Ho, Low-Tone, Jorgenson, Eric, Pesich, Robert, Chen, Yii-Der I., Dzau, Victor, Lin, Alfred, Olshen, Richard A., Curb, David, Cox, David R., Botstein, David
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 06-11-2001; National Acad Sciences; The National Academy of Sciences
• Subjects: Adult; aldosterone synthase; Base Sequence; Biological Sciences; Blood Glucose - analysis; Cytochrome P-450 CYP11B2 - genetics; Diabetes; Diabetes Mellitus - blood; Diabetes Mellitus - enzymology; Diabetes Mellitus - genetics; DNA Primers; Fasting; Female; Genetic Variation; Genetics; Genotype; Genotypes; Glucose; Glucose Tolerance Test; Homozygotes; Hormones; Humans; Hypertension; Insulin; Insulin - blood; Insulin resistance; Introns; Male; Middle Aged; Plasma; Siblings
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.221467098

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.