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

Abstract

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. Diabetes 56: 276 -280, 2007 O besity is an increasing problem in modern societies and a major risk factor for chronic diseases including diabetes, hypertension, and cardiovascular disease (1-3). Despite many genetic studies, only a small percentage of obesity cases can be directly explained by single gene mutations (4 -7).Different studies have shown a heritable component for eating behavior (8 -12). Meal size and meal frequency are two eating patterns that show heritability (8 -10). Only a few studies have been conducted to find genes underlying this heritability. Two studies have reported on genomewide linkage screens: Steinle et al. (11) showed specific logarithm of odds scores for specific eating habits and Bouchard et al. (13) reported evidence of a specific candidate gene neuromedin B for eating behaviors and predisposition to obesity. Two hormones, cholecystokinin (CCK) and leptin, have been implicated in the control of meal size and frequency in animal and human studies. Individuals with defects in the leptin gene have constant hunger and craving for food, which suggests a role for leptin in feelings of hunger in humans (14). However, mutations in leptin and its receptor explain only a very small proportion of the obese population. CCK is a satiety hormone. Administration of CCK in rats and humans results in a reduction of food intake (15-17). In contrast to leptin (receptor), no associations between obesity and the CCK gene have been described.To determine whether common genetic variations in the CCK gene, the leptin gene, and its receptor contribute to abnormal eating habits in obese women, we performed a case-control study and tested these genes for association with meal size and meal frequency in a sample of individuals displayi...

Leptin Gene and Leptin Receptor Gene Polymorphisms Are Associated with Sweet Preference and Obesity

“…Although it has been reported that genetic variations underlie specific eating patterns (14) and sweet preference is considered to be a risk factor for obesity, few reports have shown an association between them (15), and none have examined whether human LEP and LEPR polymorphisms have effects on sweet preference. However, there have been several reports indicating associations between LEP/LEPR polymorphisms and obesity (5).…”

Food-induced brain responses and eating behaviour

“…Thus, it may be worthwhile to select on more specific or additional (endo)phenotypic characteristics, such as personality characteristics or measures of eating behaviour. For example, it was shown that cholecystokinin and leptin (receptor) polymorphisms are associated with meal size and snacking frequency (77) , which makes these behavioural measures potential selection criteria for a genotype associated with 'overeating'.…”

Eating disorder/and or eating behavior researches from West Bengal, India: Suppressing the facts??

“…CCK variants (rs6809785, rs7611677, rs6801844, and rs6791019) were found to be more associated with extreme meal size, but not increased snacking behavior in the same study. This study 13 suggests that genetic variation in genes encoding CCK and leptin may contribute to obesity risk by influencing satiety. However, the research article 27 surprisingly overlooked the earlier research efforts regarding genetic variation to body weight and body shape.…”

“…CCK is released 35 in response to lipids and promotes rapid post-prandial satiety in contrast to the long term action of leptin. In a large case-control study 13 of obese and normal weight women, common leptin variants, (rs4577902, rs2060736, and rs4731413), have been found to be associated with increased risk of extreme snacking behavior (top 5th percentile based on 11 question questionnaire), but not increased meal size. CCK variants (rs6809785, rs7611677, rs6801844, and rs6791019) were found to be more associated with extreme meal size, but not increased snacking behavior in the same study.…”

“…The study of genetic variants in digestive neuroendocrine hormones, such as CCK, leptin and ghrelin, are providing new insights into how these hormones and their genetic variants may be involved in pathways regulating appetite and eating behavior. The current knowledge with respect to genetic variants linked to meal selection and size contributing to eating behaviors like, extreme snacking behavior, 13 binge eating. 14 A variety of cognitive pathways are involved in motivation and control of eating behavior.…”