Genetic vasopressin 1b receptor variance in overweight and diabetes mellitus.
OBJECTIVE
Recently, imbalance in the vasopressin (AVP) system, measured as elevated levels of copeptin (the C-terminal part of the AVP pro-hormone) in plasma, was linked to the development of abdominal obesity and diabetes mellitus (DM). Here, we aim to investigate if the genetic variation of the human AVP receptor 1b gene (AVPR1B) is associated with measures of obesity and DM.


METHODS
Malmö Diet and Cancer study (MDC) is a population-based prospective cohort examined 1991-1996.


METHODS
Four tag single nucleotide polymorphisms (SNPs: rs35810727, rs28373064, rs35439639, rs35608965) of AVPR1B were genotyped in the cardiovascular cohort (n=6103) of MDC (MDC-CC) and associated with measures of obesity and DM. Significant SNPs were replicated in another 24 344 MDC individuals (MDC replication cohort).


RESULTS
In MDC-CC, the major allele of rs35810727 was associated with elevated BMI (β-coefficient ± s.e.m.; 0.30 ± 0.14, P=0.03) and waist (0.78 ± 0.36, P=0.03) after age and gender adjustment. The association with BMI was replicated in the MDC replication cohort (0.21 ± 0.07, P=0.003), whereas that with waist was not significant. In MDC-CC there was no association between the major allele of rs35810727 and DM, but in the complete MDC cohort (n=30 447) the major allele of rs35810727 was associated with DM (OR (95% CI); 1.10 (1.00-1.20), P=0.04).


CONCLUSIONS
Genetic variance of AVPR1B contributes to overweight. Furthermore, our data indicate a link between AVPR1B variance and DM development. Our data point at a relationship between the disturbance of the pharmacologically modifiable AVP system and the body weight regulation.
Department of Clinical SciencesClinical Research Center (CRC), Skåne University Hospital, Lund University, Jan Waldenströms gata 35, Building 91, Floor 12, SE 205 02 Malmö, SwedenCenter of Emergency MedicineSkåne University Hospital, Malmö, SwedenSphingoTec GmbHHohen Neuendorf, Germany Department of Clinical SciencesClinical Research Center (CRC), Skåne University Hospital, Lund University, Jan Waldenströms gata 35, Building 91, Floor 12, SE 205 02 Malmö, SwedenCenter of Emergency MedicineSkåne University Hospital, Malmö, SwedenSphingoTec GmbHHohen Neuendorf, Germany sofia.enhorning@med.lu.se.
Sofia
S
Enhörning
Department of Clinical SciencesClinical Research Center (CRC), Skåne University Hospital, Lund University, Jan Waldenströms gata 35, Building 91, Floor 12, SE 205 02 Malmö, SwedenCenter of Emergency MedicineSkåne University Hospital, Malmö, SwedenSphingoTec GmbHHohen Neuendorf, Germany.
Marketa
M
Sjögren
Department of Clinical SciencesClinical Research Center (CRC), Skåne University Hospital, Lund University, Jan Waldenströms gata 35, Building 91, Floor 12, SE 205 02 Malmö, SwedenCenter of Emergency MedicineSkåne University Hospital, Malmö, SwedenSphingoTec GmbHHohen Neuendorf, Germany Department of Clinical SciencesClinical Research Center (CRC), Skåne University Hospital, Lund University, Jan Waldenströms gata 35, Building 91, Floor 12, SE 205 02 Malmö, SwedenCenter of Emergency MedicineSkåne University Hospital, Malmö, SwedenSphingoTec GmbHHohen Neuendorf, Germany.
Bo
B
Hedblad
Department of Clinical SciencesClinical Research Center (CRC), Skåne University Hospital, Lund University, Jan Waldenströms gata 35, Building 91, Floor 12, SE 205 02 Malmö, SwedenCenter of Emergency MedicineSkåne University Hospital, Malmö, SwedenSphingoTec GmbHHohen Neuendorf, Germany Department of Clinical SciencesClinical Research Center (CRC), Skåne University Hospital, Lund University, Jan Waldenströms gata 35, Building 91, Floor 12, SE 205 02 Malmö, SwedenCenter of Emergency MedicineSkåne University Hospital, Malmö, SwedenSphingoTec GmbHHohen Neuendorf, Germany.
Peter M
PM
Nilsson
Department of Clinical SciencesClinical Research Center (CRC), Skåne University Hospital, Lund University, Jan Waldenströms gata 35, Building 91, Floor 12, SE 205 02 Malmö, SwedenCenter of Emergency MedicineSkåne University Hospital, Malmö, SwedenSphingoTec GmbHHohen Neuendorf, Germany.
Joachim
J
Struck
Department of Clinical SciencesClinical Research Center (CRC), Skåne University Hospital, Lund University, Jan Waldenströms gata 35, Building 91, Floor 12, SE 205 02 Malmö, SwedenCenter of Emergency MedicineSkåne University Hospital, Malmö, SwedenSphingoTec GmbHHohen Neuendorf, Germany Department of Clinical SciencesClinical Research Center (CRC), Skåne University Hospital, Lund University, Jan Waldenströms gata 35, Building 91, Floor 12, SE 205 02 Malmö, SwedenCenter of Emergency MedicineSkåne University Hospital, Malmö, SwedenSphingoTec GmbHHohen Neuendorf, Germany.
Olle
O
Melander
D000368:Aged; D015992:Body Mass Index; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000235:genetics*; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006020:Glycopeptides / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics; D056128:Obesity, Abdominal / Q000235:genetics; D050177:Overweight / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011446:Prospective Studies; D017483:Receptors, Vasopressin / Q000235:genetics*; D013548:Sweden
D006020:Glycopeptides; D017483:Receptors, Vasopressin; C048197:copeptins