Secretin is a peptide hormone playing multiple functions in the brain-gut axis. In this report, we investigated, by promoter analysis, the potential function of the variable of tandem repeats (VNTR), located at the 5' upstream region of the human secretin gene, and we demonstrated for the first time that this VNTR could downregulate transcription of the human secretin gene in a promoter-specific manner. The efficiency of VNTR in silencing the promoter was found to be directly related the number of repetitive units residing within. We also showed the deoxyribonucleic acid sequence as well as the length polymorphism of the VNTR of 76 Chinese individuals. These results collectively suggest that VNTR could potentially be a functional regulator to control the expression of the human secretin gene in different individuals.