Eur J Endocrinol
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DOI: 10.1530/EJE-09-0122
European Journal of Endocrinology, Vol 161, Issue 2, 307-315
Copyright © 2009 by European Society of Endocrinology
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CLINICAL STUDY

The role of ghrelin and ghrelin-receptor gene variants and promoter activity in type 2 diabetes

Edwin A Garcia, Peter King, Kally Sidhu, Hideko Ohgusu1, Andrew Walley2, Cecile Lecoeur5, Maria Gueorguiev, Sahira Khalaf, Derek Davies4, Ashley B Grossman, Masayasu Kojima1, Stephan Petersenn3, Phillipe Froguel2,5 and Márta Korbonits

Department of Endocrinology, Barts and the London School of Medicine and Dentistry, William Harvey Research Institute, Queen Mary University of London, London EC1M 6BQ, UK1 Molecular Genetics, Institute of Life Science, Kurume University, Kurume 1-1, Japan2 Imperial College Genome Centre and Genomic Medicine, Imperial College London, Hammersmith Hospital, London W12 0NN, UK3 Division of Endocrinology, University of Duisburg-Essen, 45122 Essen, Germany4 London Research Institute Cancer Research UK, London WC2A 3PX, UK5 Centre National de la Recherche Scientifique UMR 8090-Institute of Biology, Pasteur Institute, 59000 Lille, France

(Correspondence should be addressed to M Korbonits; Email: m.korbonits{at}qmul.ac.uk)

Background: Ghrelin and its receptor play an important role in glucose metabolism and energy homeostasis, and therefore they are functional candidates for genes carrying susceptibility alleles for type 2 diabetes.

Methods: We assessed common genetic variation of the ghrelin (GHRL; five single nucleotide polymorphisms (SNP)) and the ghrelin-receptor (GHSR) genes (four SNPs) in 610 Caucasian patients with type 2 diabetes and 820 controls. In addition, promoter reporter assays were conducted to model the regulatory regions of both genes.

Results: Neither GHRL nor GHSR gene SNPs were associated with type 2 diabetes. One of the ghrelin haplotypes showed a marginal protective role in type 2 diabetes. We observed profound differences in the regulation of the GHRL gene according to promoter sequence variants. There are three different GHRL promoter haplotypes represented in the studied cohort causing up to 45% difference in the level of gene expression, while the promoter region of GHSR gene is primarily represented by a single haplotype.

Conclusion: The GHRL and GHSR gene variants are not associated with type 2 diabetes, although GHRL promoter variants have significantly different activities.






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