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Common Genetic Variations in CCK, Leptin, and Leptin Receptor Genes Are Associated With Specific Human Eating Patterns

¹ Department of Pharmacology and Anatomy, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands
² The Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands
³ Division of Biomedical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands
⁴ Department of Epidemiology and Bioinformatics, University Medical Center Groningen, University of Groningen, the Netherlands

Address correspondence and reprint requests to Dr. Mariken de Krom, Department of PharmacologyAnatomy, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, Netherlands. E-mail: m.dekrom{at}med.uu.nl

Abbreviations: CCK, cholecystokinin; EDP, extreme discordant phenotype; EPIC, European Prospective Study into Cancer and Nutrition; SNP, single nucleotide polymorphism

Obesity has a heritable component; however, the heterogeneity of obesity complicates dissection of its genetic background. In this study, we therefore focused on eating patterns as specific traits within obesity. These traits have a heritable component; genes associated with a specific eating pattern have not yet been reported at the population level. In this study, we determined whether genetic variations in cholecystokinin (CCK) and leptin genes underlie specific eating patterns. We selected obese individuals showing extreme snacking behavior or use of excessive portion sizes from a large population-based sample (n = 17,357) from the Prospect-EPIC (European Prospective Study into Cancer and Nutrition) study. Using allele-specific PCRs, we tested several single nucleotide polymorphisms in the candidate genes and performed haplotype analysis. Obese carriers of common allelic variations in leptin or the leptin receptor gene had an increased risk to display extreme snacking behavior. In contrast, obese carriers of common allelic variations in CCK had an increased risk to eating increased meal sizes. In conclusion, we identified common allelic variants specifically associated with distinctly different eating patterns, namely extreme snacking behavior or excessive portion size.

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