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Identification of a functional PRSS1 promoter variant in linkage disequilibrium with the chronic pancreatitis-protecting rs10273639
  1. Arnaud Boulling1,2,3,
  2. Masahiro Sato4,
  3. Emmanuelle Masson1,5,
  4. Emmanuelle Génin1,
  5. Jian-Min Chen1,2,3,
  6. Claude Férec1,2,3,5
  1. 1 Institut National de la Santé et de la Recherche Médicale (INSERM), Brest, France
  2. 2 Faculté de Médecine et des Sciences de la Santé, Université de Bretagne Occidentale (UBO), Brest, France
  3. 3 Etablissement Français du sang (EFS)—Bretagne, Brest, France
  4. 4 Section of Gene Expression Regulation, Frontier Science Research Center, Kagoshima University, Kagoshima, Japan
  5. 5 Laboratoire de Génétique Moléculaire et d'Histocompatibilité, Centre Hospitalier Régional Universitaire (CHRU) Brest, Hôpital Morvan, Brest, France
  1. Correspondence to Dr Arnaud Boulling, INSERM U1078, 46 rue Félix Le Dantec, Brest 29218, France; arnaud.boulling{at}inserm.fr

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We read with interest the paper by Derikx et al 1 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, we sought to establish whether the proximal promoter of PRSS1 is sufficient to drive specific gene expression. We thus constructed two luciferase reporter plasmids in the context of the two major alleles, one encompassing the two polymorphic sites …

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