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


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


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


METHODS
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.


CONCLUSIONS
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.
Lavebratt
C
C
Department of Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. catharina.lavebratt@cmm.ki.se
Alpman
A
A
Persson
B
B
Arner
P
P
Hoffstedt
J
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D001069:Appetite Regulation / Q000235:genetics; D015992:Body Mass Index; D016022:Case-Control Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics* / Q000503:physiopathology; D009767:Obesity, Morbid / Q000235:genetics / Q000503:physiopathology; D050177:Overweight / Q000235:genetics / Q000502:physiology; D019894:Peptide YY / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D017476:Receptors, Neuropeptide Y / Q000235:genetics* / Q000502:physiology
D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor; D019894:Peptide YY