{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T08:53:56Z","timestamp":1790326436447,"version":"4.1.0"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2021,5,11]],"date-time":"2021-05-11T00:00:00Z","timestamp":1620691200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,5,11]],"date-time":"2021-05-11T00:00:00Z","timestamp":1620691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Diabetologia"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Aims\/hypothesis<\/jats:title>\n                <jats:p>The incidence of type 1 diabetes is increasing more rapidly than can be explained by genetic drift. Viruses may play an important role in the disease, as they seem to activate the 2\u2032-5\u2032-linked oligoadenylate (2\u2032-5\u2032A) pathway of the innate antiviral immune system. Our aim was to investigate this possibility.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Innate antiviral immune pathways were searched for type 1 diabetes-associated polymorphisms using genome-wide association study data. SNPs within \u00b1250kb flanking regions of the transcription start site of 64 genes were examined. These pathways were also investigated for type 1 diabetes-associated RNA expression profiles using laser-dissected islets from two to five tissue sections per donor from the Diabetes Virus Detection (DiViD) study and the network of Pancreatic Organ Donors (nPOD).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We found 27 novel SNPs in genes nominally associated with type 1 diabetes. Three of those SNPs were located upstream of the 2\u2032-5\u2032A pathway, namely SNP rs4767000 (<jats:italic>p<\/jats:italic> = 1.03 \u00d7 10<jats:sup>\u22129<\/jats:sup>, OR 1.123), rs1034687 (<jats:italic>p<\/jats:italic> = 2.16 \u00d7 10<jats:sup>\u22127<\/jats:sup>, OR 0.869) and rs739744 (<jats:italic>p<\/jats:italic> = 1.03 \u00d7 10<jats:sup>\u22129<\/jats:sup>, OR 1.123). We also identified a large group of dysregulated islet genes in relation to type 1 diabetes, of which two were novel. The most aberrant genes were a group of IFN-stimulated genes. Of those, the following distinct pathways were targeted by the dysregulation (compared with the non-diabetic control group): <jats:italic>OAS1<\/jats:italic> increased by 111% (<jats:italic>p<\/jats:italic> &lt; 1.00 \u00d7 10<jats:sup>\u22124<\/jats:sup>, 95% CI \u22120.43, \u22120.15); <jats:italic>MX1<\/jats:italic> increased by 142% (<jats:italic>p<\/jats:italic> &lt; 1.00 \u00d7 10<jats:sup>\u22124<\/jats:sup>, 95% CI \u22120.52, \u22120.22); and <jats:italic>ISG15<\/jats:italic> increased by 197% (<jats:italic>p<\/jats:italic> = 2.00 \u00d7 10<jats:sup>\u22124<\/jats:sup>, 95% CI \u22120.68, \u22120.18).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions\/interpretation<\/jats:title>\n                <jats:p>We identified a genetic predisposition in the 2\u2032-5\u2032A pathway that potentially contributes to dysregulation of the innate antiviral immune system in type 1 diabetes. This study describes a potential role for the 2\u2032-5\u2032A pathway and other components of the innate antiviral immune system in beta cell autoimmunity.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical abstract<\/jats:title>\n                \n              <\/jats:sec>","DOI":"10.1007\/s00125-021-05469-5","type":"journal-article","created":{"date-parts":[[2021,5,10]],"date-time":"2021-05-10T23:58:11Z","timestamp":1620691091000},"page":"1805-1815","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Genetic predisposition in the 2\u2032-5\u2032A pathway in the development of type 1 diabetes: potential contribution to dysregulation of innate antiviral immunity"],"prefix":"10.1007","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5135-6021","authenticated-orcid":false,"given":"Kristina","family":"Pedersen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4088-5862","authenticated-orcid":false,"given":"Martin","family":"Haupt-Jorgensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Krogvold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0490-1028","authenticated-orcid":false,"given":"Simranjeet","family":"Kaur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan C.","family":"Gerling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3274-5448","authenticated-orcid":false,"given":"Flemming","family":"Pociot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6952-9899","authenticated-orcid":false,"given":"Knut","family":"Dahl-J\u00f8rgensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0126-7423","authenticated-orcid":false,"given":"Karsten","family":"Buschard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,11]]},"reference":[{"issue":"3","key":"5469_CR1","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1002\/smi.2861","volume":"35","author":"R Roth","year":"2019","unstructured":"Roth R, Lynch K, Hyoty H et al (2019) The association between stressful life events and respiratory infections during the first 4 years of life: The Environmental Determinants of Diabetes in the Young study. 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