Identification of a functional PRSS1 promoter variant in linkage disequilibrium with the chronic pancreatitis-protecting rs10273639

We read with interest the paper by Derikx et al1 replicating the association of the minor T allele of single nucleotide polymorphism rs10273639C/T, which is located 408 bp upstream of the translation initiation codon of the cationic trypsinogen (PRSS1) gene, with a protective effect against chronic pancreatitis.2 However, whether rs10273639 is the causal variant or not remains unknown. Resolving this issue is of intrinsic biological interest, and it may also have diagnostic and therapeutic value. During resequencing of the promoter region of PRSS1 in 287 French Caucasian individuals (see online supplementary material), we found that rs4726576C/A, which is located 204 bp upstream of the translation initiation codon of PRSS1 (figure 1A), is in perfect linkage disequilibrium (LD) with rs10273639C/T (figure 2A). To identify which polymorphism is of potential biological relevance, we performed a two-step luciferase promoter reporter assay (see online supplementary material). First,...

Source: Gut - October 8, 2015 Category: Gastroenterology Authors: Boulling, A., Sato, M., Masson, E., Genin, E., Chen, J.-M., Ferec, C. Tags: PostScript Source Type: research