Family and population-based studies of variation within the ghrelin receptor locus in relation to measures of obesity.
BACKGROUND
The growth hormone secretagogue receptor (GHSR) is mediating hunger sensation when stimulated by its natural ligand ghrelin. In the present study, we tested the hypothesis that common and rare variation in the GHSR locus are related to increased prevalence of obesity and overweight among Whites.


RESULTS
In a population-based study sample of 15,854 unrelated, middle-aged Danes, seven variants were genotyped to capture common variation in an 11 kbp region including GHSR. These were investigated for their individual and haplotypic association with obesity. None of these analyses revealed consistent association with measures of obesity. A -151C/T promoter mutation in the GHSR was found in two unrelated obese patients. One family presented with complete co-segregation, but the other with incomplete co-segregation. The mutation resulted in an increased transcriptional activity (p<0.02) and introduction of a specific binding for Sp-1-like nuclear extracts relative to the wild type. The -151C/T mutation was genotyped in the 15,854 Danes with a minor allele frequency of 0.01%. No association with obesity in carriers (mean BMI: 27+/-4 kg/m(2)) versus non-carriers (mean BMI: 28+/-5 kg/m(2)) (p>0.05) could be shown.


CONCLUSIONS
In a population-based study sample of 15,854 Danes no association between GHSR genotypes and measures of obesity and overweight was found. Also, analyses of GHSR haplotypes lack consistent associations with obesity related traits. A rare functional GHSR promoter mutation variant was identified, yet there was no consistent relationship with obesity in neither family- nor population-based studies.
Gjesing
Anette P
AP
Hagedorn Research Institute, Gentofte, Denmark. apri@hagedorn.dk
Larsen
Lesli H
LH
Torekov
Signe S
SS
Hainerová
Irena Aldhoon
IA
Kapur
Rahul
R
Johansen
Anders
A
Albrechtsen
Anders
A
Boj
Sylvia
S
Holst
Birgitte
B
Harper
Angela
A
Urhammer
Søren A
SA
Borch-Johnsen
Knut
K
Pisinger
Charlotta
C
Echwald
Søren M
SM
Eiberg
Hans
H
Astrup
Arne
A
Lebl
Jan
J
Ferrer
Jorge
J
Schwartz
Thue W
TW
Hansen
Torben
T
Pedersen
Oluf
O
D003718:Denmark; D005192:Family Health; D056726:Genetic Association Studies; D056426:Genetic Loci; D014644:Genetic Variation; D006801:Humans; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology / Q000235:genetics*; D050177:Overweight / Q000453:epidemiology / Q000235:genetics; D017354:Point Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics; D054440:Receptors, Ghrelin / Q000235:genetics*; D044465:White People
D054440:Receptors, Ghrelin
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