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Ghrelin Receptor Gene: Identification of Several Sequence Variants in Extremely Obese Children and Adolescents, Healthy Normal-Weight and Underweight Students, and Children with Short Normal Stature

Institute of Child and Adolescent Health (H.-J.W.), Health Science Center, Peking University, Beijing 100083, China; Clinical Research Group (H.-J.W., N.S., S.F., F.F.-H., H.R., J.H., A.H.), Department of Child and Adolescent Psychiatry, and Institute of Medical Biometry and Epidemiology (F.G., A.D., H.S.), Philipps-University of Marburg, 35039 Marburg, Germany; GSF-National Research Center for Environment and Health (P.L., T.B., T.M.), Institute of Human Genetics, 85764 Neuherberg, Germany; Center of Child and Adolescent Medicine (S.W., S.H., L.G.), Justus Liebig University, 35392 Giessen, Germany; and Department of Genome Analysis (K.H.), Institute of Molecular Biotechnology, 07745 Jena, Germany

Address all correspondence and requests for reprints to: Dr. Anke Hinney, Clinical Research Group, Department of Child and Adolescent Psychiatry, Phillips-Universtity of Marburg, Schützenstrasse 49, 35039 Marburg, Germany. E-mail: Anke.Hinney{at}med.uni-marburg.de.

GH secretagogue receptor (GHSR, ghrelin receptor) is involved in regulation of body weight and GH secretion. We initially analyzed two single-nucleotide polymorphisms of the GHSR in up to 184 extremely obese children and adolescents and up to 184 healthy underweight students. The frequency of the 171T allele of rs495225 was higher in our obese samples (75.0%) than in the underweight individuals (70.2%; nominal P = 0.14). This trend could not be substantiated in an additional association study in 270 obese and 145 underweight and normal weight individuals and in a transmission disequilibrium test based on 387 obesity trios (transmission rate of 171T, 51.8%; nominal P = 0.53). Additionally, the coding region of GHSR was systematically screened, and seven sequence variants were identified in 93 obese, 96 normal weight, and 94 underweight individuals and 43 children with short normal stature (SNS). Five silent single-nucleotide polymorphisms showed similar genotype frequencies in the different weight groups and SNS children (all nominal P > 0.3). Two novel missense variants were detected only in one obese carrier and one SNS child, respectively. In conclusion, we did not obtain conclusive evidence for an involvement of the ghrelin receptor gene in body weight regulation or SNS in our study groups.

This work was supported by the Deutsche Forschungsgemeinschaft. H.-J.W. was supported by the Gottlieb Daimler- und Karl Benz-Stiftung, and the Bundesministerium für Bildung und Forschung (BMBF) (01KW006; 01GS0118) supported the ascertainment of children with short normal stature and the biometrical analyses. The genotyping platform at the GSF is supported by BMBF/Nationales Genomforschungsnetz Grant 01GR0103.

Abbreviations: BMI, Body mass index; DHPLC, denaturing HPLC; GHS, GH secretagogue; GHSR, GHS receptor; MALDI-TOF MS, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry; RFLP, restriction fragment length polymorphism; SNP, single-nucleotide polymorphism; SNS, short normal stature; SSCP, single-strand conformational polymorphism; TDT, transmission disequilibrium test.

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