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Relation between human vasopressin 1a gene variance, fat intake, and diabetes^1,2,3

¹ From the Department of Clinical Sciences, Lund University, Malmö, Sweden (SE, ML, PW, BG, GB, EW, and OM); the Department of Internal Medicine, Malmö University Hospital, Malmö, Sweden (SE and OM); and the Department of Cardiology, Malmö University Hospital, Malmö, Sweden (ML).

² Supported by grants from the Swedish Medical Research Council, the Swedish Heart and Lung Foundation, the Medical Faculty of Lund University (Malmö University Hospital), the Albert Påhlsson Research Foundation, the Crafoord Foundation, the Ernhold Lundströms Research Foundation, the Region Skane, the Hulda and Conrad Mossfelt Foundation, the King Gustaf V and Queen Victoria Foundation, and the Lennart Hanssons Memorial Fund.

³ Address reprint requests and correspondence to S Enhörning, Department of Clinical Sciences, Clinical Research Center, Malmö University Hospital, SE-205 02 Malmö, Sweden. E-mail: sofia.enhorning{at}med.lu.se.

ABSTRACT

Background: Male arginine vasopressin 1a receptor knockout mice (V1aR^–/–) display a phenotype of low triglycerides and high glucose concentrations and high-fat-diet–induced obesity and diabetes.

Objective: We investigated whether genetic variation of the human arginine vasopressin 1A (AVPR1A) gene is associated with phenotypic features resembling those of the V1aR^–/– mouse.

Design: In a population-based cross-sectional study in southern Sweden, middle-aged individuals (n = 6055) were examined in 1991–1994. Associations between 4 AVPR1A tag single nucleotide polymorphisms (rs1042615, rs10784339, rs7308855, and rs10747983) and diabetes status, glucose and triglyceride concentrations, and BMI were analyzed. Furthermore, rs1042615 was related to diabetes status, glucose, and triglycerides within sex-specific quartiles of dietary fat intake (Q1_Fat-Q4_Fat) and BMI (Q1_BMI-Q4_BMI).

Results: Subjects carrying the T allele of rs1042615 had lower concentrations of triglycerides than did CC carriers (1.36 ± 0.77 compared with 1.42 ± 0.89 mmol/L; P = 0.014), especially in nondiabetic subjects (P = 0.001). Carriers of the rs1042615 T allele had higher fasting blood glucose (5.20 ± 1.44 mmol/L compared with 5.12 ± 1.22 mmol/L; P = 0.036) and a tendency toward an increased prevalence of diabetes (odds ratio: 1.22; 95% CI: 0.99, 1.51; P = 0.067) compared with CC carriers. The less common rs10784339, rs7308855, and rs10747983 were not consistently associated with metabolic variables. Among men, the rs1042615 T allele was associated with diabetes exclusively within Q4_Fat (odds ratio: 2.22; 95% CI: 1.05, 4.71; P = 0.04) and Q4_BMI (odds ratio: 1.81; 95% CI: 1.11, 2.93; P = 0.02).

Conclusion: The rs1042615 T allele is associated with features resembling the phenotype of the V1aR^–/– mouse, including uncoupling of the usual direct relation between glucose and triglycerides and an increased prevalence of diabetes in subjects with a high fat intake or who are overweight.

Received for publication May 7, 2008. Accepted for publication October 19, 2008.