Impact of a CART promoter genetic variation on plasma lipid profile in a general population

The cocaine and amphetamine regulated transcript (CART), an anorexigenic peptide responding to leptin, is expressed in various areas of the hypothalamus. The role of CART in humans and its potential contribution to abnormalities in feeding control are mostly unknown. Since CART plays an important role in the hypothalamic regulation of energy balance by reducing food intake and increasing lipid substrate utilization, it might affect cholesterol metabolism as Neuropeptide Y or pro-opiomelanocortin do. In the present work, we studied the potential effects of three SNPs of the CART promoter in a WHO-MONICA general population from North of France (n = 840), untreated for hypercholesterolemia, hypertension, or diabetes mellitus since any treatment is likely to interfere with lipoprotein/lipid variables. Our results show associations between these SNPs and plasma LDL-cholesterol level and the LDL/HDL ratio, a marker of atherogenicity. A haplotypic study suggests that these effects are mainly attributable to the functional SNP -3608C > T. Subjects bearing the -3608 C allele present a plasma lipid profile protective against atherogenesis: decrease of plasma LDL-cholesterol level (P = 0.001) and of the LDL/HDL ratio (p = 0.0003). This result offers new evidences for a potential implication of the CART gene in lipid metabolism and in atherogenesis. (c) 2006 Elsevier Inc. All rights reserved.