Significant association between a silent polymorphism in the neuromedin B gene and body weight in German children and adolescents.
Neuromedin B has been shown to exert an inhibiting effect on food consumption in rats. The corresponding gene NMB maps to chromosome 15q22.3-q23, a region expected to contain a gene for the Bardet-Biedl syndrome type 4 (BBS4). Based on its map position and the putative function of the encoded peptide, NMB can be considered as a candidate gene both for BBS4 and the development of human obesity. To examine its involvement in these phenotypes, we determined the genomic structure of human NMB, and performed a mutation screen in its coding region. In genomic DNA of six BBS4 patients and in a large population sample, two sequence variants were detected: a g.253C-->A transversion creating a P73T substitution and a g.401G-->A silent mutation changing the stop codon TGA into stop codon TAA. A case-control study with 92 extremely obese patients and 94 underweight students revealed a significant association between the g.401G-->A polymorphism and body weight (adjustedp = 0.03), which was confirmed in a validation sample consisting of 95 extremely obese patients, and 95 normal weight and 48 underweight individuals (Mann-Whitney p = 0.02). These results suggest a contribution of NMB or a gene in its close vicinity to genetic weight control in humans.
Oeffner
F
F
Institute of Human Genetics, Philipps-University of Marburg, Germany.
Bornholdt
D
D
Ziegler
A
A
Hinney
A
A
Görg
T
T
Gerber
G
G
Goldschmidt
H P
HP
Siegfried
W
W
Wright
A
A
Hebebrand
J
J
Grzeschik
K H
KH
D000293:Adolescent; D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence / Q000235:genetics; D020788:Bardet-Biedl Syndrome / Q000235:genetics / Q000473:pathology; D001483:Base Sequence / Q000235:genetics; D001835:Body Weight / Q000502:physiology*; D016022:Case-Control Studies; D005091:Exons / Q000235:genetics; D005787:Gene Frequency; D020868:Gene Silencing; D016678:Genome; D005838:Genotype; D006801:Humans; D008969:Molecular Sequence Data; D015287:Neurokinin B / Q000031:analogs & derivatives* / Q000235:genetics*; D009765:Obesity / Q000235:genetics* / Q000473:pathology*; D011110:Polymorphism, Genetic / Q000502:physiology*; D013851:Thinness / Q000235:genetics / Q000473:pathology
D015287:Neurokinin B; C038393:neuromedin B