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

International Journal of Obesity volume 30, pages 453–459 (2006)Cite this article

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.

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Acknowledgements

The laboratory assistance of Selim Sengul, Britt-Marie Leijonhufvud, Katarina Hertel, Eva Sjölin, Kerstin Wåhlén and Elisabeth Dungner, and the manuscript review by Martin Schalling are greatly acknowledged. This study was supported by grants from Swedish Medical Research Council, Swedish Diabetes Association and Novo Nordic Foundation.

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Authors and Affiliations

  1. Department of Molecular Medicine, Karolinska Institutet, Stockholm, Sweden

    C Lavebratt & A Alpman

  2. Centre for Genomics and Bioinformatics, Karolinska Institutet, Stockholm, Sweden

    B Persson

  3. IFM Bioinformatics, Linköping University, Linköping, Sweden

    B Persson

  4. Department of Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden

    P Arner & J Hoffstedt

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  1. C Lavebratt
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Correspondence to C Lavebratt.

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Lavebratt, C., Alpman, A., Persson, B. et al. Common neuropeptide Y2 receptor gene variant is protective against obesity among Swedish men. Int J Obes 30, 453–459 (2006). https://doi.org/10.1038/sj.ijo.0803188

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