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


METHODS
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.


RESULTS
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.


CONCLUSIONS
Common variants rs12649641, rs2342676 and rs6857530 in the 5' region of NPY2R are associated with obesity in Danish white subjects.
Torekov
S S
SS
Steno Diabetes Center, Niels Steensens Vej 2, 2820 Gentofte, Denmark. skto@steno.dk
Larsen
L H
LH
Andersen
G
G
Albrechtsen
A
A
Glümer
C
C
Borch-Johnsen
K
K
Jørgensen
T
T
Hansen
T
T
Pedersen
O
O
D020121:5' Untranslated Regions / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D049628:Body Size; D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D003718:Denmark; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D015810:Linkage Disequilibrium; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017476:Receptors, Neuropeptide Y / Q000235:genetics*; D044465:White People / Q000235:genetics*
D020121:5' Untranslated Regions; D001786:Blood Glucose; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor; D004247:DNA