Among the five POMC SNPs, rs1866146, which is located in the downstream region, showed the most significant result. Although this variant does not change POMC peptide sequence or modify subsequent protein cleavage, given its positive association with substance dependence (this study) and obesity traits (20), we cannot exclude the possibility that it regulates POMC transcription. By querying the sequence harboring rs1866146 against the Transcription Element Search System (TESS) database TRANSFAC v6.0 (http://www.cbil.upenn.edu/tess), we found that the core binding site (GCCTC) of transcription factor T-Ag harbors the minor allele (C) [rather than the major allele (T)] of rs1866146. TRANSFAC analysis is considered provisional since prediction of transcription factor binding sites is far from full-proof.
