Family and population-based studies of variation within the ghrelin receptor locus in relation to measures of obesity

Research output: Contribution to journalJournal articleResearchpeer-review


  • Family...

    Final published version, 299 KB, PDF document

  • Anette P. Gjesing
  • Lesli Hingstrup Larsen
  • Irena Aldhoon Hainerová
  • Rahul Kapur
  • Anders Johansen
  • Sylvia Boj
  • Angela Harper
  • Søren A. Urhammer
  • Knut Borch-Johnsen
  • Charlotta Holm Pisinger
  • Søren M Echwald
  • Arne Astrup
  • Jan Lebl
  • Jorge Ferrer
  • Torben Hansen
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. METHODOLOGY/PRINCIPAL FINDINGS: 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/SIGNIFICANCE: 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.
Original languageEnglish
JournalP L o S One
Issue number4
Number of pages8
Publication statusPublished - 2010

Number of downloads are based on statistics from Google Scholar and

No data available

ID: 23372092