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dc.contributor.authorTraherne, Jamesen
dc.contributor.authorJiang, Weien
dc.contributor.authorValdes, Ana Mariaen
dc.contributor.authorHollenbach, Jill Aen
dc.contributor.authorJayaraman, Jyothien
dc.contributor.authorLane, Julie Aen
dc.contributor.authorJohnson, Chrisen
dc.contributor.authorTrowsdale, Johnen
dc.contributor.authorNoble, Janelle Aen
dc.date.accessioned2015-09-18T15:00:41Z
dc.date.available2015-09-18T15:00:41Z
dc.date.issued2015-10-22en
dc.identifier.citationTraherne et al. Genes and Immunity (2016), 17(1), pp. 8–12. doi: 10.1038/gene.2015.44en
dc.identifier.issn1466-4879
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/251069
dc.description.abstractClassical human leukocyte antigens (HLA) genes confer the strongest, but not the only, genetic susceptibility to type 1 diabetes. Killer cell immunoglobulin-like receptors (KIR), on natural killer (NK) cells, bind ligands including class I HLA. We examined presence or absence, with copy number, of KIR loci in 1698 individuals, from 339 multiplex type 1 diabetes families, from the Human Biological Data Interchange, previously genotyped for HLA. Combining family data with KIR copy number information allowed assignment of haplotypes using identity by descent. This is the first disease study to use KIR copy number typing and unambiguously define haplotypes by gene transmission. KIR A1 haplotypes were positively associated with T1D in the subset of patients without the high T1D risk HLA genotype, DR3/DR4 (odds ratio=1.29, P=0.0096). The data point to a role for KIR in type 1 diabetes risk in late-onset patients. In the top quartile (age of onset>14), KIR A2 haplotype was overtransmitted (63.4%, odds ratio=1.73, P=0.024) and KIR B haplotypes were undertransmitted (41.1%, odds ratio=0.70, P=0.0052) to patients. The data suggest that inhibitory ‘A’ haplotypes are predisposing and stimulatory ‘B’ haplotypes confer protection in both DR3/DR4-negative and late-onset patient groups.
dc.description.sponsorshipThis work was supported in part by National Institutes of Health award R01 DK61722 (J.A.N.). Research in the Trowsdale lab is supported by the MRC and Wellcome Trust with part funding from the National Institute for Health Research Cambridge Biomedical Research Centre.
dc.languageEnglishen
dc.language.isoenen
dc.publisherNature Publishing Group
dc.rightsAttribution 2.0 UK: England & Wales
dc.rights.urihttp://creativecommons.org/licenses/by/2.0/uk/
dc.subjectType 1 diabetesen
dc.subjectKIRen
dc.subjectHLAen
dc.titleKIR haplotypes are associated with late-onset type 1 diabetes in European–American familiesen
dc.typeArticle
dc.description.versionThis is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/gene.2015.44en
prism.endingPage12
prism.publicationDate2015en
prism.publicationNameGenes and Immunityen
prism.startingPage8
prism.volume17en
dc.rioxxterms.funderNIH
dc.rioxxterms.funderMRC
dc.rioxxterms.funderWellcome Trust
dc.rioxxterms.funderNIHR
dc.rioxxterms.projectidR01 DK61722
dcterms.dateAccepted2015-09-15en
rioxxterms.versionofrecord10.1038/gene.2015.44en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2015-10-22en
dc.contributor.orcidTraherne, James [0000-0002-6003-8559]
dc.contributor.orcidJiang, Wei [0000-0002-6119-3331]
dc.contributor.orcidTrowsdale, John [0000-0002-0150-5698]
dc.identifier.eissn1476-5470
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (G0901682)
pubs.funder-project-idWellcome Trust (100140/Z/12/Z)


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Attribution 2.0 UK: England & Wales
Except where otherwise noted, this item's licence is described as Attribution 2.0 UK: England & Wales