The associations of the C825T polymorphism (rs5443) of the G-protein beta 3 subunit (GNB3) gene and eight adjacent single nucleotide polymorphisms (SNPs) with diabetes were examined using a Japanese population (n (M/W): 2956 (1335/1621): age: 63.0 +/- 10.2 years). Fasting plasma glucose (FPG) levels were significantly associated with the C825T polymorphism and two flanking SNPs (rs2301339 and rs5446) (p = 0.002, 0.001, and 0.008, respectively). A case-control association Study of the C825T polymorphism with diabetes using multiple logistic regression analysis showed a significant association of the genotypes TT + TC with an odds ratio of 0.62 (p = 0.008) independent of age, gender, and BMI. The effects of salt consumption on the association were then examined (n = 1635). The FPG levels were significantly associated with the C825T polymorphism only in subjects with low salt consumption (<12.44 g/day) (p = 0.002). A case-control association study also showed a significant association with diabetes only in subjects with low salt consumption (p = 0.006). (C) 2008 Elsevier Inc. All rights reserved.