Alcohol-dependent effect of PRSS1-PRSS2 haplotype in chronic pancreatitis

We read with great interest the studies by Derikx et al ,1 Boulling et al 2 and Masson et al ,3 in which the authors report that a commonly occurring haplotype spanning the PRSS1-PRSS2 locus (encoding human cationic and anionic trypsinogen) is associated with chronic pancreatitis with an allelic OR of 0.7 in European cohorts (figure 1). Tagged by the c.-408C>T variant (rs10273639), this haplotype was first identified in a GWAS by the Whitcomb laboratory.4 The small but significant protective effect is likely due to the c.-204C>A promoter variant (rs4726576) in PRSS1 , which decreases trypsinogen expression and thereby reduces the risk of premature trypsin activation in the pancreas.2 Curiously, Derikx et al 1 found a clear association of the PRSS1-PRSS2 haplotype with alcoholic pancreatitis only, whereas no association was evident with non-alcoholic disease. Whitcomb et al also noted that the effect of the haplotype seemed to be amplified by alcohol.4 The French study did not specify disease aetiology.2 …