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  • PRSS1 copy number variants and promoter polymorphisms in pancreatitis: common pathogenetic mechanism, different genetic effects

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PRSS1 copy number variants and promoter polymorphisms in pancreatitis: common pathogenetic mechanism, different genetic effects
  1. Emmanuelle Masson1,2,
  2. Jian-Min Chen1,3,
  3. David N Cooper4,
  4. Claude Férec1,2,3,5
  1. 1 Institut National de la Santé et de la Recherche Médicale (INSERM), U1078 Brest, France
  2. 2 Laboratoire de Génétique Moléculaire et d’Histocompatibilité, Centre Hospitalier Universitaire (CHU) Brest, Hôpital Morvan, Brest, France
  3. 3 Etablissement Français du Sang (EFS) – Bretagne, Brest, France
  4. 4 Faculté de Médecine et des Sciences de la Santé, Université de Bretagne Occidentale (UBO), Brest, France
  5. 5 Institute of Medical Genetics, School of Medicine, Cardiff University, Cardiff, UK
  1. Correspondence to Dr Jian-Min Chen, INSERM U1078, EFS–Bretagne, 46 rue Félix Le Dantec, 29218 Brest, France; jian-min.chen{at}univ-brest.fr

https://doi.org/10.1136/gutjnl-2017-314443

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    We have read with interest three related papers that were recently published in this journal.1–3 Taken together, the findings reported in these papers (summarised in online supplementary note) suggest that loss-of-function PRSS1 promoter variants can protect against pancreatitis. The other side of the coin is however that gain-of-function PRSS1 promoter variants predispose to pancreatitis. It therefore follows that the risk-associated [rs4726576C; rs10273639C] allele shares a common pathogenetic mechanism with the previously reported trypsinogen duplication and triplication copy number variants (CNVs)4 5 as both types of variant predispose to pancreatitis by increasing PRSS1 expression; this mechanism is quite distinct from either the increased activation and/or stability of trypsin(ogen) or misfolding-induced endoplasmic reticulum stress caused by disease-associated PRSS1 missense mutations.6 However, despite both serving to increase PRSS1 expression, the promoter variant and the CNVs differ significantly in terms of the …

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