[Show abstract][Hide abstract] ABSTRACT: Arginine vasopressin (AVP), a peptide hormone released from the posterior pituitary, has been suggested to play important roles in cardiovascular regulation, glycogenolysis and platelet aggregation through its V1a receptor (V1aR). In this study, we investigated the association of 4 novel single nucleotide polymorphisms (SNPs) in V1aR gene (-6951G/A, -4112A/T, -3860T/C and -242C/T) with hypertension, diabetes mellitus (DM) and glycemic status, and platelet responsiveness to AVP. Genotypes were determined in 365 hypertensives and 255 healthy subjects, 186 patients with type 2 DM (T2DM) and 188 non-diabetic control subjects (CS), and 33 young healthy subjects in the Aomori prefecture. A significant association was found between the SNP -6951G/A and hypertension in nonobese individuals. Multiple logistic analysis demonstrated SNP -6951G/A as an independent risk factor for nonobese hypertension. One haplotype H3 (a-a-c-c) was characteristic to hypertension in nonobese. A significant association was found between the SNP -6951G/A and type 2 DM. Logistic regression also confirmed the significant association of the SNP -6951G/A with type 2 DM. There were a couple of characteristic distributions of heterozygous haplotype combinations in T2DM. In young healthy subjects, GA+AA carriers of SNP -6951 showed significantly higher HbAlc levels than in GG. Platelet aggregation responses to AVP were identical between wild types and variants of any SNPs. These results suggest that -6951G/A SNP and haplotypes created by 4 SNPs of V1aR gene might confer susceptibility to essential hypertension in nonobese individuals and type 2 DM. However, these SNPs might not be useful as genetic marker for platelet aggregation heterogeneity.