Sequence variants in the human cocaine and amphetamine-regulated transcript (CART) gene in subjects with early onset obesity

Objective: The cocaine and amphetamine-regulated transcript (CART) is expre ssed in the brain of rodents and humans, and intracerebroventricular inject ion of the peptide in rats reduces food intake. The objective of the presen t study was to chromosomally map the CART gene and to examine the coding re gion of the gene for variability in obese subjects. Methods: The coding region of the CART gene was analyzed by single-strand c onformation polymorphism analysis in 84 subjects with early onset obesity. The prevalence of identified mutations was estimated in a cohort of 757 sub jects with juvenile onset obesity [body mass index (BMI)=35.7+/-5.7 kg/m(2) +/-standard deviation (S)] and in 890 random control subjects (BMI=26.1+/-3 .6 kg/m(2)+/-S). Furthermore, using radiation hybrid mapping we mapped the chromosomal localization of the human CART gene. Results: Radiation hybrid mapping co-localized the CART gene with a recentl y published human obesity locus at chromosome 5q13-14 corresponding also to an obesity locus at the similar syntenic region in mice. We identified two silent polymorphisms in the 3'UTR region of the gene (position 1457 deleti on of A and position 1475 A-->G substitution) and the prevalence of these w as determined among obese and control subjects, However, none of the varian ts were associated with either obesity or weight gain during an average fol low-up period of 27.4+/-8.4 years (S). Conclusion: Mutations in the coding region of the CART gene are unlikely to be involved in body weight control in Danish Caucasians with early onset o besity.