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

Anette P. Gjesing; Lesli Hingstrup Larsen; Signe Sørensen Torekov; Irena Aldhoon Hainerová; Rahul Kapur; Anders Johansen; Anders Albrechtsen; Sylvia Boj; Birgitte Holst; Angela Harper; Søren A. Urhammer; Knut Borch-Johnsen; Charlotta Holm Pisinger; Søren M Echwald; Hans Rudolf Lytchoff Eiberg; Arne Astrup; Jan Lebl; Jorge Ferrer; Thue W. Schwartz; Torben Hansen; Oluf Pedersen

doi:10.1371/journal.pone.0010084

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

Anette P. Gjesing, Lesli Hingstrup Larsen, Signe Sørensen Torekov, Irena Aldhoon Hainerová, Rahul Kapur, Anders Johansen, Anders Albrechtsen, Sylvia Boj, Birgitte Holst, Angela Harper, Søren A. Urhammer, Knut Borch-Johnsen, Charlotta Holm Pisinger, Søren M Echwald, Hans Rudolf Lytchoff Eiberg, Arne Astrup, Jan Lebl, Jorge Ferrer, Thue W. Schwartz, Torben HansenOluf Pedersen

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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. 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±64 kg/m²) versus non-carriers (mean BMI: 28±65 kg/m2) (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 language	English
Journal	P L o S One
Volume	5
Issue number	4
Number of pages	8
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0010084
Publication status	Published - 2010

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Gjesing, A. P., Larsen, L. H., Torekov, S. S., Hainerová, I. A., Kapur, R., Johansen, A., Albrechtsen, A., Boj, S., Holst, B., Harper, A., Urhammer, S. A., Borch-Johnsen, K., Pisinger, C. H., Echwald, S. M., Eiberg, H. R. L., Astrup, A., Lebl, J., Ferrer, J., Schwartz, T. W., ... Pedersen, O. (2010). Family and population-based studies of variation within the ghrelin receptor locus in relation to measures of obesity. P L o S One, 5(4). https://doi.org/10.1371/journal.pone.0010084

Gjesing, AP, Larsen, LH, Torekov, SS, Hainerová, IA, Kapur, R, Johansen, A, Albrechtsen, A, Boj, S, Holst, B, Harper, A, Urhammer, SA, Borch-Johnsen, K, Pisinger, CH, Echwald, SM, Eiberg, HRL, Astrup, A, Lebl, J, Ferrer, J, Schwartz, TW, Hansen, T & Pedersen, O 2010, 'Family and population-based studies of variation within the ghrelin receptor locus in relation to measures of obesity', P L o S One, vol. 5, no. 4. https://doi.org/10.1371/journal.pone.0010084

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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. 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±64 kg/m2) versus non-carriers (mean BMI: 28±65 kg/m2) (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.",

author = "Gjesing, {Anette P.} and Larsen, {Lesli Hingstrup} and Torekov, {Signe S{\o}rensen} and Hainerov{\'a}, {Irena Aldhoon} and Rahul Kapur and Anders Johansen and Anders Albrechtsen and Sylvia Boj and Birgitte Holst and Angela Harper and Urhammer, {S{\o}ren A.} and Knut Borch-Johnsen and Pisinger, {Charlotta Holm} and Echwald, {S{\o}ren M} and Eiberg, {Hans Rudolf Lytchoff} and Arne Astrup and Jan Lebl and Jorge Ferrer and Schwartz, {Thue W.} and Torben Hansen and Oluf Pedersen",

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year = "2010",

doi = "10.1371/journal.pone.0010084",

language = "English",

volume = "5",

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T1 - Family and population-based studies of variation within the ghrelin receptor locus in relation to measures of obesity

AU - Gjesing, Anette P.

AU - Larsen, Lesli Hingstrup

AU - Torekov, Signe Sørensen

AU - Hainerová, Irena Aldhoon

AU - Kapur, Rahul

AU - Johansen, Anders

AU - Albrechtsen, Anders

AU - Boj, Sylvia

AU - Holst, Birgitte

AU - Harper, Angela

AU - Urhammer, Søren A.

AU - Borch-Johnsen, Knut

AU - Pisinger, Charlotta Holm

AU - Echwald, Søren M

AU - Eiberg, Hans Rudolf Lytchoff

AU - Astrup, Arne

AU - Lebl, Jan

AU - Ferrer, Jorge

AU - Schwartz, Thue W.

AU - Hansen, Torben

AU - Pedersen, Oluf

N1 - Paper id:: e10084

PY - 2010

Y1 - 2010

N2 - 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±64 kg/m2) versus non-carriers (mean BMI: 28±65 kg/m2) (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.

AB - 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±64 kg/m2) versus non-carriers (mean BMI: 28±65 kg/m2) (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.

U2 - 10.1371/journal.pone.0010084

DO - 10.1371/journal.pone.0010084

M3 - Journal article

C2 - 20404923

SN - 1932-6203

VL - 5

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 4

ER -

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

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