Open Access Research article

Analysis of sequence variability in the CART gene in relation to obesity in a Caucasian population

Audrey Guérardel1, Mouna Barat-Houari1, Francis Vasseur12, Christian Dina1, Vincent Vatin1, Karine Clément3, Delphine Eberlé3, Valérie Vasseur-Delannoy1, Christopher G Bell7, Pilar Galan4, Serge Hercberg4, Nicole Helbecque5, Natascha Potoczna6, Fritz F Horber6, Philippe Boutin1 and Philippe Froguel7*

Author Affiliations

1 Institute of Biology-CNRS UMR 8090, Pasteur Institute, Lille, France

2 University Hospital, Lille, France

3 Department of Nutrition-EA3502, Paris VI University, INSERM "Avenir" Hôtel-Dieu, Paris, France

4 Scientific and Technical Institute of Nutrition and Food (ISTNA-CNAM), INSERM U557, INRA U1125, Paris, France

5 Service d'Epidémiologie et de Santé Publique-INSERM U.508, Pasteur Institute, Lille, France

6 Dr. Horber Adipositas Stiftung, Hornbachstrasse 50, 8034, Zürich, Switzerland

7 Imperial College genome Centre and Genomic Medicine, Hammersmith Campus, Imperial College London, UK

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BMC Genetics 2005, 6:19  doi:10.1186/1471-2156-6-19

Published: 11 April 2005

Abstract

Background

Cocaine and amphetamine regulated transcript (CART) is an anorectic neuropeptide located principally in hypothalamus. CART has been shown to be involved in control of feeding behavior, but a direct relationship with obesity has not been established. The aim of this study was to evaluate the effect of polymorphisms within the CART gene with regards to a possible association with obesity in a Caucasian population.

Results

Screening of the entire gene as well as a 3.7 kb region of 5' upstream sequence revealed 31 SNPs and 3 rare variants ; 14 of which were subsequently genotyped in 292 French morbidly obese subjects and 368 controls. Haplotype analysis suggested an association with obesity which was found to be mainly due to SNP-3608T>C (rs7379701) (p = 0.009). Genotyping additional cases and controls also of European Caucasian origin supported further this possible association between the CART SNP -3608T>C T allele and obesity (global p-value = 0.0005). Functional studies also suggested that the SNP -3608T>C could modulate nuclear protein binding.

Conclusion

CART SNP -3608T>C may possibly contribute to the genetic risk for obesity in the Caucasian population. However confirmation of the importance of the role of the CART gene in energy homeostasis and obesity will require investigation and replication in further populations.