Relation between human vasopressin 1a gene variance, fat intake, and diabetes.
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.


METHODS
In a population-based cross-sectional study in southern Sweden, middle-aged individuals (n = 6,055) 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).


CONCLUSIONS
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.
Enhörning
Sofia
S
Department of Clinical Sciences, Lund University, Malmö, Sweden. sofia.enhorning@med.lu.se
Leosdottir
Margret
M
Wallström
Peter
P
Gullberg
Bo
B
Berglund
Göran
G
Wirfält
Elisabet
E
Melander
Olle
O
D000483:Alleles; D000818:Animals; D001120:Arginine / Q000235:genetics; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D004041:Dietary Fats / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D011446:Prospective Studies; D017483:Receptors, Vasopressin / Q000235:genetics*; D014280:Triglycerides / Q000097:blood*
D001786:Blood Glucose; D004041:Dietary Fats; D017483:Receptors, Vasopressin; D014280:Triglycerides; D001120:Arginine