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Diabetologia
Published in: Diabetologia 3/2007

01-03-2007 | Article

Single nucleotide polymorphisms in the neuropeptide Y2 receptor (NPY2R) gene and association with severe obesity in French white subjects

Authors: A. Siddiq, M. Gueorguiev, C. Samson, S. Hercberg, B. Heude, C. Levy-Marchal, B. Jouret, J. Weill, D. Meyre, A. Walley, P. Froguel

Published in: Diabetologia | Issue 3/2007

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Abstract

Aims/hypothesis

Genetic variants of genes for peptide YY (PYY), neuropeptide Y2 receptor (NPY2R) and pancreatic polypeptide (PPY) were investigated for association with severe obesity.

Subjects and methods

The initial screening of the genes for variants was performed by sequencing in a group of severely obese subjects (n = 161). Case-control analysis of the common variants was then carried out in 557 severely obese adults, 515 severely obese children and 1,163 non-obese/non-diabetic control subjects. Rare variants were genotyped in 700 obese children and the non-obese/non-diabetic control subjects (n = 1,163).

Results

Significant association was found for a 5′ variant (rs6857715) in the NPY2R gene with both severe adult obesity (p = 0.002) and childhood obesity (p = 0.02). This significant association was further supported by a pooled allelic analysis of all obese cases (adults and children, n = 928) vs the control subjects (n = 938) (p = 0.0004, odds ratio = 1.3, 95% CI 1.1–1.5). Quantitative trait analysis of BMI and WHR was performed and significant association was observed for SNP rs1047214 in NPY2R with an increase in WHR in the severely obese children (co-dominant model p = 0.005, recessive model p = 0.001). Association was also observed for an intron 3 variant (rs162430) in the PYY gene with childhood obesity (p = 0.04). No significant associations were observed for PPY variants. Only one rare variant in the NPY2R gene (C-5641T) was not found in lean individuals and this was found to co-segregate with obesity in one family.

Conclusions/interpretation

These results provide evidence of association for NPY2R and PYY gene variants with obesity and none for PPY variants. A rare variant of the NPY2R gene showed evidence of co-segregation with obesity and its contribution to obesity should be investigated further.
Appendix
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Literature
1.
Korner J, Leibel RL (2003) To eat or not to eat—how the gut talks to the brain. N Engl J Med 349:926–928PubMedCrossRef
2.
Erlanson-Albertsson C (2005) How palatable food disrupts appetite regulation. Basic Clin Pharmacol Toxicol 97:61–73PubMedCrossRef
3.
Ramos EJ, Meguid MM, Campos AC, Coelho JC (2005) Neuropeptide Y, alpha-melanocyte-stimulating hormone, and monoamines in food intake regulation. Nutrition 21:269–279PubMedCrossRef
4.
5.
Adrian TE, Ferri GL, Bacarese-Hamilton AJ, Fuessl HS, Polak JM, Bloom SR (1985) Human distribution and release of a putative new gut hormone, peptide YY. Gastroenterology 89:1070–1077PubMed
6.
Batterham RL, Cowley MA, Small CJ et al (2002) Gut hormone PYY(3–36) physiologically inhibits food intake. Nature 418:650–654PubMedCrossRef
7.
Ekblad E, Sundler F (2002) Distribution of pancreatic polypeptide and peptide YY. Peptides 23:251–261PubMedCrossRef
8.
Hort Y, Baker E, Sutherland GR, Shine J, Herzog H (1995) Gene duplication of the human peptide YY gene (PYY) generated the pancreatic polypeptide gene (PPY) on chromosome 17q21.1. Genomics 26:77–83PubMedCrossRef
9.
Grandt D, Teyssen S, Schimiczek M et al (1992) Novel generation of hormone receptor specificity by amino terminal processing of peptide YY. Biochem Biophys Res Commun 186:1299–1306PubMedCrossRef
10.
Grandt D, Schimiczek M, Beglinger C et al (1994) Two molecular forms of peptide YY (PYY) are abundant in human blood: characterization of a radioimmunoassay recognizing PYY 1–36 and PYY 3–36. Regul Pept 51:151–159PubMedCrossRef
11.
Grandt D, Schimiczek M, Struk K et al (1994) Characterization of two forms of peptide YY, PYY(1–36) and PYY(3–36), in the rabbit. Peptides 15:815–820PubMedCrossRef
12.
Batterham RL, Cohen MA, Ellis SM et al (2003) Inhibition of food intake in obese subjects by peptide YY3–36. N Engl J Med 349:941–948PubMedCrossRef
13.
Pittner RA, Moore CX, Bhavsar SP et al (2004) Effects of PYY[3–36] in rodent models of diabetes and obesity. Int J Obes Relat Metab Disord 28:963–971PubMedCrossRef
14.
Vrang N, Madsen AN, Tang-Christensen M, Hansen G, Larsen PJ (2006) PYY(3–36) reduces food intake and body weight and improves insulin sensitivity in rodent models of diet-induced obesity. Am J Physiol Regul Integr Comp Physiol 291:R367–R375PubMed
15.
Adams SH, Lei C, Jodka CM et al (2006) PYY[3–36] administration decreases the respiratory quotient and reduces adiposity in diet-induced obese mice. J Nutr 136:195–201PubMed
16.
Chelikani PK, Haver AC, Reidelberger RD (2005) Intravenous infusion of peptide YY(3–36) potently inhibits food intake in rats. Endocrinology 146:879–888PubMedCrossRef
17.
Boey D, Lin S, Karl T et al (2006) Peptide YY ablation in mice leads to the development of hyperinsulinaemia and obesity. Diabetologia 49:1360–1370PubMedCrossRef
18.
Moran TH, Smedh U, Kinzig KP, Scott KA, Knipp S, Ladenheim EE (2005) Peptide YY(3–36) inhibits gastric emptying and produces acute reductions in food intake in rhesus monkeys. Am J Physiol Regul Integr Comp Physiol 288:R384–R388PubMed
19.
le Roux CW, Batterham RL, Aylwin SJ et al (2006) Attenuated peptide YY release in obese subjects is associated with reduced satiety. Endocrinology 147:3–8PubMedCrossRef
20.
Doggrell SA (2004) Can food intake be reduced with peptide YY3–36? Expert Opin Investig Drugs 13:285–287PubMedCrossRef
21.
Degen L, Oesch S, Casanova M et al (2005) Effect of peptide YY3–36 on food intake in humans. Gastroenterology 129:1430–1436PubMedCrossRef
22.
Tschop M, Castaneda TR, Joost HG et al (2004) Physiology: does gut hormone PYY3–36 decrease food intake in rodents? Nature 430:1 p following 165; discussion 2 p following 165PubMedCrossRef
23.
Boggiano MM, Chandler PC, Oswald KD et al (2005) PYY3–36 as an anti-obesity drug target. Obes Rev 6:307–322PubMedCrossRef
24.
Broberger C, Landry M, Wong H, Walsh JN, Hokfelt T (1997) Subtypes Y1 and Y2 of the neuropeptide Y receptor are respectively expressed in pro-opiomelanocortin- and neuropeptide-Y-containing neurons of the rat hypothalamic arcuate nucleus. Neuroendocrinology 66:393–408PubMed
25.
Naveilhan P, Hassani H, Canals JM et al (1999) Normal feeding behavior, body weight and leptin response require the neuropeptide Y Y2 receptor. Nat Med 5:1188–1193PubMedCrossRef
26.
Perusse L, Rice T, Chagnon YC et al (2001) A genome-wide scan for abdominal fat assessed by computed tomography in the Quebec Family Study. Diabetes 50:614–621PubMed
27.
Marco J, Zulueta MA, Correas I, Villanueva ML (1980) Reduced pancreatic polypeptide secretion in obese subjects. J Clin Endocrinol Metab 50:744–747PubMedCrossRef
28.
Lassmann V, Vague P, Vialettes B, Simon MC (1980) Low plasma levels of pancreatic polypeptide in obesity. Diabetes 29:428–430PubMed
29.
Uhe AM, Szmukler GI, Collier GR, Hansky J, O’Dea K, Young GP (1992) Potential regulators of feeding behavior in anorexia nervosa. Am J Clin Nutr 55:28–32PubMed
30.
Asakawa A, Inui A, Yuzuriha H et al (2003) Characterization of the effects of pancreatic polypeptide in the regulation of energy balance. Gastroenterology 124:1325–1336PubMedCrossRef
31.
Zipf WB, O’Dorisio TM, Cataland S, Sotos J (1981) Blunted pancreatic polypeptide responses in children with obesity of Prader–Willi syndrome. J Clin Endocrinol Metab 52:1264–1266PubMed
32.
Asakawa A, Inui A, Ueno N, Fujimiya M, Fujino MA, Kasuga M (1999) Mouse pancreatic polypeptide modulates food intake, while not influencing anxiety in mice. Peptides 20:1445–1448PubMedCrossRef
33.
Batterham RL, Le Roux CW, Cohen MA et al (2003) Pancreatic polypeptide reduces appetite and food intake in humans. J Clin Endocrinol Metab 88:3989–3992PubMedCrossRef
34.
Reinehr T, Enriori PJ, Harz K, Cowley MA, Roth CL (2006) Pancreatic polypeptide in obese children before and after weight loss. Int J Obes (Lond) 30:1476–1481CrossRef
35.
Ma L, Tataranni PA, Hanson RL et al (2005) Variations in peptide YY and Y2 receptor genes are associated with severe obesity in Pima Indian men. Diabetes 54:1598–1602PubMed
36.
Hung CC, Pirie F, Luan J et al (2004) Studies of the peptide YY and neuropeptide Y2 receptor genes in relation to human obesity and obesity-related traits. Diabetes 53:2461–2466PubMed
37.
Lavebratt C, Alpman A, Persson B, Arner P, Hoffstedt J (2006) Common neuropeptide Y2 receptor gene variant is protective against obesity among Swedish men. Int J Obes (Lond) 30:453–459CrossRef
38.
Barroso I, Luan J, Middelberg RP et al (2003) Candidate gene association study in type 2 diabetes indicates a role for genes involved in beta-cell function as well as insulin action. PLoS Biol 1:E20PubMedCrossRef
39.
Torekov SS, Larsen LH, Glumer C et al (2005) Evidence of an association between the Arg72 allele of the peptide YY and increased risk of type 2 diabetes. Diabetes 54:2261–2265PubMed
40.
Ahituv N, Kavaslar N, Schackwitz W et al (2006) A PYY Q62P variant linked to human obesity. Hum Mol Genet 15:387–391PubMedCrossRef
41.
Poskitt EM (1995) Defining childhood obesity: the relative body mass index (BMI). European Childhood Obesity group. Acta Paediatr 84:961–963PubMed
42.
Bell CG, Meyre D, Samson C et al (2005) Association of melanin-concentrating hormone receptor 1 5′ polymorphism with early-onset extreme obesity. Diabetes 54:3049–3055PubMed
43.
Rozen S (2000) Primer3 on the WWW for general users and for biologist programmers. Humana, Totowa, NJ
44.
Bell CG, Meyre D, Samson C et al (2005) Association of melanin-concentrating hormone receptor 1 5′ polymorphism with early-onset extreme obesity. Diabetes 54:3049–3055PubMed
45.
Jurinke C, van den Boom D, Cantor CR, Koster H (2002) Automated genotyping using the DNA MassArray technology. Methods Mol Biol 187:179–192PubMed
46.
Abecasis GR, Cookson WO (2000) GOLD—graphical overview of linkage disequilibrium. Bioinformatics 16:182–183PubMedCrossRef
47.
Dudbridge F (2003) Pedigree disequilibrium tests for multilocus haplotypes. Genet Epidemiol 25:115–121PubMedCrossRef
48.
Nyholt DR (2004) A simple correction for multiple testing for single-nucleotide polymorphisms in linkage disequilibrium with each other. Am J Hum Genet 74:765–769PubMedCrossRef
49.
Purcell S, Cherny SS, Sham PC (2003) Genetic Power Calculator: design of linkage and association genetic mapping studies of complex traits. Bioinformatics 19:149–150PubMedCrossRef
50.
Sainsbury A, Schwarzer C, Couzens M et al (2002) Important role of hypothalamic Y2 receptors in body weight regulation revealed in conditional knockout mice. Proc Natl Acad Sci USA 99:8938–8943PubMedCrossRef
51.
Abbott CR, Small CJ, Kennedy AR et al (2005) Blockade of the neuropeptide Y Y2 receptor with the specific antagonist BIIE0246 attenuates the effect of endogenous and exogenous peptide YY(3–36) on food intake. Brain Res 1043:139–144PubMedCrossRef
52.
Renshaw D, Batterham RL (2005) Peptide YY: a potential therapy for obesity. Curr Drug Targets 6:171–179PubMed
Metadata
Title
Single nucleotide polymorphisms in the neuropeptide Y2 receptor (NPY2R) gene and association with severe obesity in French white subjects
Authors
A. Siddiq
M. Gueorguiev
C. Samson
S. Hercberg
B. Heude
C. Levy-Marchal
B. Jouret
J. Weill
D. Meyre
A. Walley
P. Froguel
Publication date
01-03-2007
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 3/2007
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-006-0555-2

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