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


CONCLUSIONS
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.
Guérardel
Audrey
A
Institute of Biology-CNRS UMR 8090, Pasteur Institute, Lille, France. audrey@good.ibl.fr
Barat-Houari
Mouna
M
Vasseur
Francis
F
Dina
Christian
C
Vatin
Vincent
V
Clément
Karine
K
Eberlé
Delphine
D
Vasseur-Delannoy
Valérie
V
Bell
Christopher G
CG
Galan
Pilar
P
Hercberg
Serge
S
Helbecque
Nicole
N
Potoczna
Natascha
N
Horber
Fritz F
FF
Boutin
Philippe
P
Froguel
Philippe
P
D001483:Base Sequence; D016022:Case-Control Studies; D005838:Genotype; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009765:Obesity / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D044465:White People / Q000235:genetics*; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
D009419:Nerve Tissue Proteins; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein