Clarifying the clinical relevance of SPINK1 intronic variants in chronic pancreatitis

Recently, we reported the identification of a functional PRSS1 promoter variant in perfect linkage disequilibrium (LD) with the chronic pancreatitis (CP)-‘protective’ rs10273639.1 This, together with several other recent papers published in Gut,2–4 underscored the importance of functional analysis for improving our understanding of the underlying pathophysiological mechanisms and also more fundamentally for establishing the clinical relevance or otherwise of CP-associated variants from the outset. In many diseases, in vitro functional analysis often represents the only practical means to determine the pathogenicity of patient-derived sequence variants, particularly when they are rare. Herein, we present a new and successful example in the context of CP. SPINK1 is one of the most extensively studied CP genes, with >100 variants being reported to date.5 Of 19 known intronic variants, the four in LD with the p.Asn34Ser variant have been functionally analysed in the...

Source: Gut - April 7, 2016 Category: Gastroenterology Authors: Zou, W.-B., Boulling, A., Masson, E., Cooper, D. N., Liao, Z., Li, Z.-S., Ferec, C., Chen, J.-M. Tags: PostScript Source Type: research