Polymorphisms at PRSS1-PRSS2 and CLDN2-MORC4 loci associate with alcoholic and non-alcoholic chronic pancreatitis in a European replication study
Por:
Derikx, MH, Kovacs, P, Scholz, M, Masson, E, Chen, JM, Ruffert, C, Lichtner, P, te Morsche, RHM, Cavestro, GM, Ferec, C, Drenth, JPH, Witt, H, Rosendahl, J, Mora, J, PanEuropean Working Grp Alcoholic
Publicada:
1 sep 2015
Resumen:
Objective Several genetic risk factors have been identified for non-alcoholic chronic pancreatitis (NACP). A genome-wide association study reported an association of chronic pancreatitis (CP) with variants in PRSS1-PRSS2 (rs10273639; near the gene encoding cationic trypsinogen) and CLDN2-MORC4 loci (rs7057398 in RIPPLY1 and rs12688220 in MORC4). We aimed to refine these findings in a large European cohort.
Design We studied 3062 patients with alcohol-related CP (ACP) or NACP and 5107 controls. Also, 1559 German patients with alcohol-associated cirrhosis or alcohol dependence were included for comparison. We performed several meta-analyses to examine genotype-phenotype relationships.
Results Association with ACP was found for rs10273639 (OR, 0.63; 95% CI 0.55 to 0.72). ACP was also associated with variants rs7057398 and rs12688220 in men (OR, 2.26; 95% CI 1.94 to 2.63 and OR, 2.66; 95% CI 2.21 to 3.21, respectively) and in women (OR, 1.57; 95% CI 1.14 to 2.18 and OR 1.71; 95% CI 1.41 to 2.07, respectively). Similar results were obtained when German patients with ACP were compared with those with alcohol-associated cirrhosis or alcohol dependence. In the overall population of patients with NACP, association with rs10273639 was absent (OR, 0.93; 95% CI 0.79 to 1.01), whereas rs7057398 of the X chromosomal single nucleotide polymorphisms was associated with NACP in women only (OR, 1.32; 95% CI 1.15 to 1.51).
Conclusions The single-nucleotide polymorphisms rs10273639 at the PRSS1-PRSS2 locus and rs7057398 and rs12688220 at the CLDN2-MORC4 locus are associated with CP and strongly associate with ACP, but only rs7057398 with NACP in female patients.
Filiaciones:
Derikx, MH:
Radboud UMC, Dept Gastroenterol & Hepatol, Nijmegen, Netherlands
Kovacs, P:
Univ Leipzig, Integrated Res & Treatment Ctr IFB Adipos Dis, D-04109 Leipzig, Germany
Scholz, M:
Univ Leipzig, Inst Med Informat Stat & Epidemiol, D-04109 Leipzig, Germany
Univ Leipzig, LIFE Leipzig Res Ctr Civilizat Dis, D-04109 Leipzig, Germany
Masson, E:
INSERM, U1078, Brest, France
Etab Francais Sang EFS Bretagne, Brest, France
Univ Bretagne Occidentale, Fac Med & Sci Sante, Brest, France
CHU Brest, Hop Morvan, Lab Genet Mol & Histocompatibil, F-29285 Brest, France
Chen, JM:
INSERM, U1078, Brest, France
Etab Francais Sang EFS Bretagne, Brest, France
Univ Bretagne Occidentale, Fac Med & Sci Sante, Brest, France
CHU Brest, Hop Morvan, Lab Genet Mol & Histocompatibil, F-29285 Brest, France
Ruffert, C:
Univ Leipzig, Dept Internal Med Neurol & Dermatol, Div Gastroenterol & Rheumatol, D-04109 Leipzig, Germany
Lichtner, P:
German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Inst Human Genet, Neuherberg, Germany
te Morsche, RHM:
Radboud UMC, Dept Gastroenterol & Hepatol, Nijmegen, Netherlands
Cavestro, GM:
Univ Vita Salute San Raffaele, Unita Operat Gastroenterol & Endoscopia Digest, Milan, Italy
IRCCS, Osped San Raffaele, Milan, Italy
Ferec, C:
INSERM, U1078, Brest, France
Etab Francais Sang EFS Bretagne, Brest, France
Univ Bretagne Occidentale, Fac Med & Sci Sante, Brest, France
CHU Brest, Hop Morvan, Lab Genet Mol & Histocompatibil, F-29285 Brest, France
Drenth, JPH:
Radboud UMC, Dept Gastroenterol & Hepatol, Nijmegen, Netherlands
Witt, H:
Zent Inst Ernahrungs & Lebensmittelforsch, Else Kroner Fresenius Zentrum Ernahrungsmed EKFZ, Munich, Germany
Tech Univ Munich, Paediat Nutr Med, D-80290 Munich, Germany
Rosendahl, J:
Univ Leipzig, Dept Internal Med Neurol & Dermatol, Div Gastroenterol & Rheumatol, D-04109 Leipzig, Germany
Mora, J:
Department of Biochemistry, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
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