{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:58:58Z","timestamp":1790175538741,"version":"4.1.0"},"reference-count":21,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2019,3,20]],"date-time":"2019-03-20T00:00:00Z","timestamp":1553040000000},"content-version":"vor","delay-in-days":29,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Investissements d\u2019Avenir programme","award":["ANR-11-IDEX-0005-02"],"award-info":[{"award-number":["ANR-11-IDEX-0005-02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,9,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background and Aims<\/jats:title>\n                  <jats:p>Nucleotide Oligomerisation Domain 2 [NOD2] is a key gene of innate immunity which participates in the host defence against pathogens. Several loss-of-function NOD2 mutations are associated with Crohn\u2019s disease [CD]. Their high frequencies in populations of European ancestry suggest a model of balancing selection. Because NOD2 deficiency has been associated with a resistance to Yersinia pseudotuberculosis in mice, we hypothesised that NOD2 mutations have been selected during past plague outbreaks due to the closely related bacterium Yersinia pestis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Contemporary frequencies of the main CD-associated NOD2 mutations [R702W, G908R, and 1007fs], measured in healthy people from European and Mediterranean countries, were collected from 60 studies via a PubMed search. Plague exposure was calculated from a dataset providing outbreaks from 1346 to 1860 in Europe and the Mediterranean Bassin. A plague index was built to capture the intensity of plague exposure in the studied geographical areas.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>NOD2 mutation frequencies were associated with the past exposure to plague. Statistical significance was obtained for the most frequent mutation [R702W, p = 0.03] and for the pooled three mutations [p = 0.023]. The association remained significant when putative demographic biases were considered.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This result argues for a selection of CD-associated NOD2 mutations by plague outbreaks and further questioned the role of exposure to enteropathogenic Yersinia species in CD.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ecco-jcc\/jjz062","type":"journal-article","created":{"date-parts":[[2019,3,19]],"date-time":"2019-03-19T21:07:33Z","timestamp":1553029653000},"page":"1318-1322","source":"Crossref","is-referenced-by-count":12,"title":["Is Crohn\u2019s Disease the Price to Pay Today for Having Survived the Black Death?"],"prefix":"10.1093","volume":"13","author":[{"given":"Anne","family":"Dumay","sequence":"first","affiliation":[{"name":"Research Centre on Inflammation, UMR1149 INSERM, Universit\u00e9 Paris Diderot, Sorbonne-Paris-Cit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Gergaud","sequence":"additional","affiliation":[{"name":"KEDGE Business School, Bordeaux and LIEPP, Sciences Po, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryline","family":"Roy","sequence":"additional","affiliation":[{"name":"Research Centre on Inflammation, UMR1149 INSERM, Universit\u00e9 Paris Diderot, Sorbonne-Paris-Cit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Pierre","family":"Hugot","sequence":"additional","affiliation":[{"name":"Research Centre on Inflammation, UMR1149 INSERM, Universit\u00e9 Paris Diderot, Sorbonne-Paris-Cit\u00e9, Paris, France"},{"name":"H\u00f4pital Robert Debr\u00e9, Assistance Publique H\u00f4pitaux de Paris, DHU Unity, Paris, 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