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Association between Neuromedin U Gene Variants and Overweight and Obesity

Department of Pediatrics and Centre for Research of Diabetes, Metabolism, and Nutrition (I.H., M.F., J.L.), Third Faculty of Medicine, Charles University, 100 34 Prague 10, Czech Republic; Steno Diabetes Center and Hagedorn Research Institute (S.S.T., J.E., K.B.-J., O.D.M., T.H., O.P.), DK-2820 Gentofte, Denmark; Kennedy Institute-National Eye Clinic (J.E.), DK-2600 Glostrup, Denmark; Research Center for Prevention and Health (T.J.), Glostrup University Hospital, DK-2600 Glostrup, Denmark; and Faculty of Health (K.B.-J., O.P.), University of Aarhus, DK-8000 Aarhus, Denmark

Address all correspondence and requests for reprints to: Irena Hainerová, M.D., Department of Pediatrics, robárova 50, 100 34 Prague 10, Czech Republic. E-mail: ihainer{at}hotmail.com.

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.

Design: 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.

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

Subjects and 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 25 kg/m²) [odds ratio, 2.5 (1.2–5.3); P = 0.01].

Conclusion: Amino acid variants in NMU associate with overweight and obesity, suggesting that NMU is involved in energy regulation in humans.

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