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We read with great interest the studies by Derikx et al,1 Boulling et al2 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 al1 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 …
PH and MS-T contributed equally.
Contributors Study concept and design: EH and MS-T. Genotyping experiments: AZT and EH. Acquisition, analysis and interpretation of data: all authors. Drafting of the manuscript: EH and MS-T. Critical revision of the manuscript for important intellectual content: all authors. Obtained funding: EH, PH and MS-T. Administrative, technical or material support: all authors. Study supervision: EH, PH and MS-T. Final approval of the manuscript as submitted: all authors. Guarantors of the article: EH, PH and MS-T.
Funding This study was supported by the National Institutes of Health grant R01 DK058088 (to MS-T) and a National Pancreas Foundation research grant (to EH). EH was also supported by the National Scholarship Programme of the Slovak Republic, the János Bolyai Research Scholarship and the Premier Postdoctoral Scholarship of the Hungarian Academy of Sciences. PH, AV, AS and the registry and biobank of the Hungarian Pancreatic Study Group was supported by project grants (KH125678 and K116634 to PH), the Economic Development and Innovation Operative Programme Grant (GINOP 2.3.2-15-372 2016–00048 to PH) and the Human Resources Development Operational Programme Grant (EFOP-3.6.2-16-2017-00006 to PH) from the National Research Development and Innovation Office of Hungary.
Competing interests None declared.
Patient consent for publication Not required.
Ethical approval. Experiments were performed at Boston University. Deidentified genomic DNA samples were obtained from the registry of the Hungarian Pancreatic Study Group (ethical approval: TUKEB 22254-1/2012/EKU, biobanking approval: IF702-19/2012). Individuals in the registry were recruited from 11 Hungarian centres between 2012 and 2016, and all gave informed consent according to the ethical guidelines of the Declaration of Helsinki. The study was approved by the institutional review board (IRB) at Boston University ('Analysis of susceptibility genes in patients with chronic pancreatitis', IRB number H-35382).
Provenance and peer review Not commissioned; internally peer reviewed.
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