title: Family and population-based studies of variation within the ghrelin receptor locus in relation to measures of obesity.
abstract: 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.
authors.affiliation: Hagedorn Research Institute, Gentofte, Denmark. apri@hagedorn.dk
authors.forename: Anette P
authors.initials: AP
authors.lastname: Gjesing
authors.forename: Lesli H
authors.initials: LH
authors.lastname: Larsen
authors.forename: Signe S
authors.initials: SS
authors.lastname: Torekov
authors.forename: Irena Aldhoon
authors.initials: IA
authors.lastname: Hainerová
authors.forename: Rahul
authors.initials: R
authors.lastname: Kapur
authors.forename: Anders
authors.initials: A
authors.lastname: Johansen
authors.forename: Anders
authors.initials: A
authors.lastname: Albrechtsen
authors.forename: Sylvia
authors.initials: S
authors.lastname: Boj
authors.forename: Birgitte
authors.initials: B
authors.lastname: Holst
authors.forename: Angela
authors.initials: A
authors.lastname: Harper
authors.forename: Søren A
authors.initials: SA
authors.lastname: Urhammer
authors.forename: Knut
authors.initials: K
authors.lastname: Borch-Johnsen
authors.forename: Charlotta
authors.initials: C
authors.lastname: Pisinger
authors.forename: Søren M
authors.initials: SM
authors.lastname: Echwald
authors.forename: Hans
authors.initials: H
authors.lastname: Eiberg
authors.forename: Arne
authors.initials: A
authors.lastname: Astrup
authors.forename: Jan
authors.initials: J
authors.lastname: Lebl
authors.forename: Jorge
authors.initials: J
authors.lastname: Ferrer
authors.forename: Thue W
authors.initials: TW
authors.lastname: Schwartz
authors.forename: Torben
authors.initials: T
authors.lastname: Hansen
authors.forename: Oluf
authors.initials: O
authors.lastname: Pedersen
mesh_terms: 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
chemical_list: D054440:Receptors, Ghrelin
references.citation: J Clin Invest. 2006 Mar;116(3):760-8
references.pmid: 16511605
references.citation: Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):581-4
references.pmid: 11136232
references.citation: Diabetes. 2005 Jan;54(1):259-67
references.pmid: 15616037
references.citation: Obesity (Silver Spring). 2009 Apr;17(4):745-54
references.pmid: 19165163
references.citation: Cent Eur J Public Health. 2004 Sep;12(3):126-30
references.pmid: 15508410
references.citation: Trends Pharmacol Sci. 2004 Mar;25(3):113-7
references.pmid: 15058279
references.citation: J Clin Invest. 2006 Mar;116(3):637-41
references.pmid: 16511600
references.citation: Curr Opin Pharmacol. 2002 Dec;2(6):665-8
references.pmid: 12482728
references.citation: Gut. 2003 Jul;52(7):947-52
references.pmid: 12801949
references.citation: Br J Nutr. 2006 Aug;96(2):201-26
references.pmid: 16923214
references.citation: Am J Hum Genet. 2002 Feb;70(2):425-34
references.pmid: 11791212
references.citation: J Psychosom Res. 1985;29(1):71-83
references.pmid: 3981480
references.citation: J Clin Invest. 2002 Jun;109(11):1429-36
references.pmid: 12045256
references.citation: Eur J Cardiovasc Prev Rehabil. 2003 Oct;10(5):377-86
references.pmid: 14663300
references.citation: Nature. 1999 Dec 9;402(6762):656-60
references.pmid: 10604470
references.citation: Obes Res. 2005 Mar;13(3):381-490
references.pmid: 15833932
references.citation: Int J Obes Relat Metab Disord. 2000 Sep;24 Suppl 3:S6-11
references.pmid: 11063279
references.citation: Am J Clin Nutr. 1997 Apr;65(4):895-907
references.pmid: 9094870