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Ghrelin Receptor Gene Polymorphisms and Body Size in Children and Adults

Department of Endocrinology (E.A.G., M.G., Z.K.H.-S., A.S., M.K.), John Vane Science Centre, Barts and the London Medical School, London EC1M 6BQ, United Kingdom; Medical Research Council Epidemiology Unit (B.H., N.W., M.S.S., K.K.O.), Institute of Metabolic Science, and Department of Paediatrics (C.J.P., D.B.D., K.K.O.), University of Cambridge, Addenbrooke’s Hospital, Cambridge CB0 0QQ, United Kingdom; Institut National de la Santé et de la Recherche Médicale Unit 780 (B.H.), Institut Fédératif de Recherche 69, Villejuif F-94807, France; Faculty of Medicine (B.H.), Université Paris-Sud, Orsay F-91405, France; and Department of Social Medicine (S.M.R.), University of Bristol, Bristol BS8 1TQ, United Kingdom

Address all correspondence and requests for reprints to: Dr. Ken Ong, Medical Research Council Epidemiology Unit, Institute of Metabolic Science, Addenbrooke’s Hospital Box 285, Cambridge CB2 0QQ, United Kingdom. E-mail: ken.ong{at}mrc-epid.cam.ac.uk.

Background: The GH secretagogue receptor type 1a gene (GHSR) encodes the cognate receptor of ghrelin, a gut hormone that regulates food intake and pituitary GH secretion. Previous studies in U.S. families and a German population suggested GHSR to be a candidate quantitative locus for association with human obesity and growth.

Aim: The aim of the study was to test common genetic variation in GHSR for association with body size in children and adults.

Methods: Sequencing was performed to systematically identify novel single nucleotide polymorphisms (SNPs) in GHSR. A set of three haplotype-tagging SNPs that captured all the genetic variation in GHSR was identified. These three haplotype-tagging SNPs were then genotyped in three large population-based U.K. cohort studies (two adult and one childhood cohort) comprising 5807 adults and 843 children.

Results: No significant genotype or haplotype associations were found with adult or childhood height, weight, or body mass index.

Conclusion: Common variation in GHSR is not associated with body size in U.K. adults or children.