Variants in the 5' region of the neuropeptide Y receptor Y2 gene (NPY2R) are associated with obesity in 5,971 white subjects

• Published in: Diabetologia Vol. 49; no. 11; pp. 2653 - 2658
• Main Authors: TOREKOV, S. S, LARSEN, L. H, ANDERSEN, G, ALBRECHTSEN, A, GLÜMER, C, BORCH-JOHNSEN, K, JØRGENSEN, T, HANSEN, T, PEDERSEN, O
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01-11-2006; Springer Nature B.V
• Subjects: 5' Untranslated Regions - genetics; Age; Aged; Aged, 80 and over; Biological and medical sciences; Blood Glucose - metabolism; Body Mass Index; Body Size; Denmark; Diabetes; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - genetics; Diabetes. Impaired glucose tolerance; DNA - blood; DNA - genetics; DNA - isolation & purification; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Epidemiology; Etiopathogenesis. Screening. Investigations. Target tissue resistance; European Continental Ancestry Group - genetics; Genetic Variation; Glucose; Humans; Hypothalamus; Hypotheses; Linkage Disequilibrium; Medical sciences; Metabolic diseases; Middle Aged; Mutation; Nervous system; Neuropeptides; Obesity; Obesity - blood; Obesity - genetics; Overweight; Peptides; Polymorphism, Single Nucleotide; Receptors, Neuropeptide Y - genetics; White people; Denmark; Aarhus Denmark; Endocrinopathy; Type 2 diabetes; Human; Obesity; Genetic/epidemiology, Genetics of type 2 diabetes, Hormone receptors; Nutrition disorder; Metabolic diseases; Epidemiology; Y2 neuropeptide Y receptor; Variant; Gene; Weight regulation and obesity; Genetics; Nutritional status; Hormonal receptor
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-006-0425-y

The gene encoding neuropeptide Y receptor Y2 (NPY2R) is widely expressed in the central nervous system, with particularly high abundance in the hypothalamus, which is known to be important for appetite regulation. We tested whether variations in NPY2R are associated with obesity.
The coding region of NPY2R was analysed for mutations in 48 obese Danish white subjects and two silent substitutions were identified: SNPs 1 and 2 (rs1047214 and rs2880415). SNP1 and additional reported variants (SNPs 3-6 [rs11099992, rs12649641, rs2342676 and rs6857530]) located in the 5' region were examined in 5,971 Danish white subjects. Since SNPs 1-2 and 4-6, respectively, were in tight linkage disequilibrium large-scale analyses of genetic epidemiology were restricted to SNPs 1, 3 and 4.
Homozygous carriers of the minor A allele of SNP4 were more common among obese subjects; the AA frequency was 15.9 (95% CI 15.2-16.6) among 4,837 non-obese subjects (BMI <30 kg/m(2)) vs 19.0 (95% CI 17.2-20.8) among 960 obese subjects (BMI > or =30 kg/m(2)), odds ratio 1.24 (95% CI 1.04-1.48), p=0.02. SNPs 1-3 were not associated with obesity.
Common variants rs12649641, rs2342676 and rs6857530 in the 5' region of NPY2R are associated with obesity in Danish white subjects.