{"doi":"10.1016/j.pan.2022.06.258","title":"Loss-of-function variant in chymotrypsin like elastase 3B (CELA3B) is associated with non-alcoholic chronic pancreatitis","abstract":"BACKGROUND: Genetic alterations in digestive enzymes have been associated with chronic pancreatitis (CP). Recently, chymotrypsin like elastase 3B (CELA3B) emerged as a novel risk gene. Thus, we evaluated CELA3B in two European cohorts with CP. METHODS: We analyzed all 8 CELA3B exons in 550 German non-alcoholic CP (NACP) patients and in 241 German controls by targeted DNA sequencing. In addition, we analyzed exons 6 and 7 by Sanger sequencing and the c.129+1G>A variant by melting curve analysis in 1078 further German controls. As replication cohort, we investigated up to 243 non-German European NACP patients and up to 1665 controls originating from Poland, Hungary, and Sweden. We assessed the cellular secretion and the elastase activity of recombinant CELA3B variants. RESULTS: In the German discovery cohort, we detected a splice-site variant in intron 2, c.129+1G>A, in 9/550 (1.64%) CP patients and in 5/1319 (0.38%) controls (P=0.007, OR=4.4, 95% CI=1.5-13.0). In the European replication cohort, this variant was also enriched in patients (9/178 [5.06%]) versus controls (13/1247 [1.04%]) (P=0.001, OR=5.1, 95% CI=2.1-12.0). We did not find the two previously reported codon 90 variants, p.R90C and p.R90L. CONCLUSIONS: Our data indicate that CELA3B is a susceptibility gene for CP. In contrast to previous reports suggesting that increased CELA3B activity is associated with CP risk, the splice-site variant identified here is predicted to cause diminished CELA3B expression. How reduced CELA3B function predisposes to pancreatitis remains to be elucidated.","journal":"Pancreatology","year":2022,"id":269675,"datarank":0.41588830833596724,"base_score":2.772588722239781,"endowment":2.772588722239781,"self_citation_contribution":0.41588830833596724,"citation_network_contribution":0.0,"self_endowment_contribution":0.41588830833596724,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9428,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":707920,"name":"Alexandra Demcsák","orcid":"0000-0002-5391-6931","position":1,"is_corresponding":false},{"id":933361,"name":"Florence Zankl","orcid":null,"position":2,"is_corresponding":false},{"id":932893,"name":"Grzegorz Oracz","orcid":"0000-0003-1938-7519","position":3,"is_corresponding":false},{"id":932894,"name":"Lara Unger","orcid":"0009-0001-2662-4650","position":4,"is_corresponding":false},{"id":719048,"name":"Peter Bugert","orcid":"0000-0002-2001-3904","position":5,"is_corresponding":false},{"id":89434,"name":"Helmut Laumen","orcid":"0000-0002-5885-5242","position":6,"is_corresponding":false},{"id":621335,"name":"Andrea Párniczky","orcid":"0000-0003-3466-4780","position":7,"is_corresponding":false},{"id":932895,"name":"Péter Hegyi","orcid":"0000-0002-4333-265X","position":8,"is_corresponding":false},{"id":451232,"name":"Jonas Rosendahl","orcid":"0000-0003-4513-0506","position":9,"is_corresponding":false},{"id":36490,"name":"Tomasz Gambin","orcid":"0000-0002-0941-4571","position":10,"is_corresponding":false},{"id":21573,"name":"Rafał Płoski","orcid":"0000-0001-6286-5526","position":11,"is_corresponding":false},{"id":932896,"name":"Dorota Kozieł","orcid":"0000-0001-8114-1814","position":12,"is_corresponding":false},{"id":919840,"name":"Stanisław Głuszek","orcid":"0000-0001-7752-0459","position":13,"is_corresponding":false},{"id":932897,"name":"Fredrik Lindgren","orcid":"0000-0001-7984-7754","position":14,"is_corresponding":false},{"id":564272,"name":"Matthias Löhr","orcid":"0000-0002-7647-198X","position":15,"is_corresponding":false},{"id":506353,"name":"Miklós Sahin‐Tóth","orcid":"0000-0003-4513-9922","position":16,"is_corresponding":false},{"id":919839,"name":"Heiko Witt","orcid":"0000-0001-7791-7341","position":17,"is_corresponding":false},{"id":919841,"name":"Agnieszka Magdalena Rygiel","orcid":"0000-0002-3838-2900","position":18,"is_corresponding":false},{"id":932898,"name":"Maren Ewers","orcid":"0000-0002-9029-2240","position":19,"is_corresponding":false},{"id":775749,"name":"Eszter Hegyi","orcid":"0000-0002-9137-7561","position":20,"is_corresponding":false},{"id":932892,"name":"Andrea E. 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