SCREENING FOR VARIABILITY IN THE CILIARY NEUROTROPHIC FACTOR (CNTF) GENE - NO EVIDENCE FOR ASSOCIATION WITH HUMAN OBESITY

Systemic administration of the neurocytokine ciliary neurotrophic fact or (CNTF) normalizes the obese phenotype of ob/ob and db/db mice. CNTF exerts its multiple effects through a receptor complex whose sequence , localization in hypothalamic nuclei and mode of signal transduction share remarkable similarities with the leptin receptor. In the human C NTF gene, a mutation in the first intron creates a new splice acceptor site, with the resulting mRNA coding for an aberrant protein (Takahas hi et al., 1994). Given the potential of CNTF to influence energy home ostasis, this study was undertaken to determine whether variability in the CNTF gene is associated with human obesity. The previously descri bed mutation was found in 30.3% of obese children and adolescents, 7 o f which were homozygous (allele frequency 0.163). 29.5% of lean subjec ts carried the mutation, none of which were homozygous (allele frequen cy 0.148; corrected p = 1 compared to obese). No further mutations wer e detected by single strand conformational polymorphism (SSCP) analysi s. In conclusion, variants in the CNTF gene are unlikely to be associa ted with the development of early-onset obesity.