Association between neuromedin U gene variants and overweight and obesity.
BACKGROUND
Neuromedin U (NMU) is an anorexic neuropeptide expressed in the hypothalamus. Mice lacking the NmU gene are hyperphagic and obese, whereas mice overexpressing Nmu are hypophagic and lean.


OBJECTIVE
Our objective was to investigate whether variants in NMU are associated with human obesity.


METHODS
The coding region of NMU was analyzed for variants in obese Czech children and obese Danish adults. Identified missense variants were investigated for cosegregation with obesity in families or association with obesity in the general population.


METHODS
The study was performed at Steno Diabetes Center, Denmark, and Department of Pediatrics, Charles University, Czech Republic.


METHODS
A total of 289 Czech children and adolescents with early-onset obesity and 84 Danish obese adults were analyzed for variants in NMU. A NMU Ala19Glu polymorphism was genotyped in 5851 Danish subjects of the Inter99 cohort, and a rare NMU Arg165Trp mutation was sequenced in the proband family and in 53 lean and unrelated Czech subjects.


RESULTS
The rare NMU Arg165Trp variant cosegregated with childhood obesity in a Czech family. Homozygous carriers of the Glu allele of the NMU Ala19Glu polymorphism were more common in the overweight and obese subjects; the Glu/Glu frequency was 0.4 (95% confidence interval, 0.2-0.6) among 2586 lean subjects (BMI < 25 kg/m2) and 0.9 (95% confidence interval, 0.7-1.1) among 3265 overweight and obese subjects (body mass index >or= 25 kg/m2) [odds ratio, 2.5 (1.2-5.3); P = 0.01].


CONCLUSIONS
Amino acid variants in NMU associate with overweight and obesity, suggesting that NMU is involved in energy regulation in humans.
Hainerová
Irena
I
Department of Pediatrics, Carles University, Czech Republic. ihainer@hotmail.com
Torekov
Signe S
SS
Ek
Jakob
J
Finková
Marie
M
Borch-Johnsen
Knut
K
Jørgensen
Torben
T
Madsen
Ole D
OD
Lebl
Jan
J
Hansen
Torben
T
Pedersen
Oluf
O
D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000235:genetics*; D009765:Obesity / Q000235:genetics*; D050177:Overweight / Q000235:genetics*; D010375:Pedigree
D009479:Neuropeptides; C056900:neuromedin U