Original Article

International Journal of Obesity (2006) 30, 453–459. doi:10.1038/sj.ijo.0803188; published online 6 December 2005

Common neuropeptide Y2 receptor gene variant is protective against obesity among Swedish men

C Lavebratt1, A Alpman1, B Persson2,3, P Arner4 and J Hoffstedt4

  1. 1Department of Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
  2. 2Centre for Genomics and Bioinformatics, Karolinska Institutet, Stockholm, Sweden
  3. 3IFM Bioinformatics, Linköping University, Linköping, Sweden
  4. 4Department of Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden

Correspondence: Dr C Lavebratt, Neurogenetics Unit, Department of Molecular Medicine, Center for Molecular Medicine Karolinska, Karolinska Institutet, Karolinska Hospital L8:00, Stockholm 171 76, Sweden. E-mail: catharina.lavebratt@cmm.ki.se

Received 1 May 2005; Revised 20 September 2005; Accepted 7 October 2005; Published online 6 December 2005.

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Abstract

Background:

 

Gut hormones and their receptors are considered important in the control of feeding behavior. The gut hormone peptide-YY (PYY) has anorexic effects via the inhibitory neuropeptide Y2 receptor (Y2R) highly expressed in orexigenic NPY/AGRP neurons within the arcuate nucleus, a major integrator of appetite control in the hypothalamus.

Design:

 

Genetic case–control association study of single nucleotide polymorphisms (SNPs) in Y2R and PYY.

Subjects:

 

Swedish Caucasians comprising 148 lean, 129 overweight/obese and 226 morbidly obese men.

Measurements:

 

Genotypes of the common, silent and conserved SNP Y2R 585T>C and the common SNP PYY Arg72Thr, as well as various obesity-related clinical parameters.

Results:

 

Obese men had a lower allele and homozygosity frequency of the common allele 585T>C:T which was particularly evident comparing morbidly obese with lean men (P=0.002), and analyzing dependence between continuous body mass index (BMI) and genotype (P=0.002). In agreement, systolic blood pressure tended to be lower in those homozygous for allele T, which was not explained by the BMI – genotype dependence. We found no association to obesity for the PYY Arg72Thr polymorphism, which is located nearby the essential carboxy terminal.

Conclusion:

 

A common and conserved variant of the PYY and NPY receptor Y2R is less prevalent among obese compared to among lean Swedish men. This suggests that the common Y2R variant is protective against obesity. Our findings further implicate Y2R in food intake regulation.

Keywords:

NPY2R, PYY, polymorphism, SNP, genetics, hypothalamus

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