Show simple item record

dc.contributor.authorNakimuli, Annetteeen
dc.contributor.authorChazara, Olympeen
dc.contributor.authorHiby, Susan Een
dc.contributor.authorFarrell, Lydiaen
dc.contributor.authorTukwasibwe, Stephenen
dc.contributor.authorJayaraman, Jyothien
dc.contributor.authorTraherne, Jamesen
dc.contributor.authorTrowsdale, Johnen
dc.contributor.authorColucci, Francescoen
dc.contributor.authorLougee, Emmaen
dc.contributor.authorVaughan, Robert Wen
dc.contributor.authorElliott, Alison Men
dc.contributor.authorByamugisha, Josaphaten
dc.contributor.authorKaleebu, Pontianoen
dc.contributor.authorMirembe, Florenceen
dc.contributor.authorNemat-Gorgani, Nedaen
dc.contributor.authorParham, Peteren
dc.contributor.authorNorman, Paul Jen
dc.contributor.authorMoffett, Ashleyen
dc.date.accessioned2015-02-17T16:00:05Z
dc.date.available2015-02-17T16:00:05Z
dc.date.issued2015-01-05en
dc.identifier.citationA Nakimuli, O Chazara, SE Hiby, L Farrell, S Tukwasibwe, J Jayaraman, JA Traherne, J Trowsdale, F Colucci, Emma Lougee, RW Vaughan, AM Elliott, J Byamugishaa, P Kaleebu, F Mirembe, N Nemat-Gorgani, P Parham, PJ Norman, A Moffett, PNAS 2015, 112, 845-850en
dc.identifier.issn0027-8424
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/246835
dc.description.abstractIn Sub-Saharan Africans, maternal mortality is unacceptably high with >400 deaths/100,000 births compared to <10/100,000 in Europeans. One third of the deaths are caused by pre-eclampsia, a syndrome arising from defective placentation. Controlling placentation are maternal natural killer cells that use killer-cell immunoglobulin-like receptors (KIR) to recognize the fetal HLA-C molecules on invading trophoblast. We analysed genetic polymorphisms of maternal KIR and fetal HLA-C for 484 normal and 254 preeclamptic pregnancies at Mulago Hospital, Kampala, Uganda. The combination of maternal KIR AA and fetal HLA-C2 associates with pre-eclampsia (P=0.0318, OR 1.49). The KIR genes associated with protection are located in centromeric KIR B regions that are unique to Sub-Saharan African populations and contain the KIR2DS5 and KIR2DL1 genes (P=0.0095, OR 0.59). By contrast, telomeric KIR B genes protect Europeans against pre-eclampsia. Thus, different KIR B regions protect Sub-Saharan Africans and Europeans from pre-eclampsia, whereas in both populations the KIR AA genotype is a risk factor for the syndrome. These results emphasize the importance of undertaking genetic studies of pregnancy disorders in African populations with the potential to provide biological insights not available from studies restricted to European populations.
dc.description.sponsorshipThis work was supported by the Wellcome Trust (090108/Z/09/Z, 085992/Z/08/Z, 089821/Z/09/Z), the British Heart Foundation (PG/ 09/077/27964), the Centre for Trophoblast Research at the University of Cambridge, a Wellcome Trust Uganda PhD Fellowship in Infection and Immunity held by Annettee Nakimuli, funded by a Wellcome Trust Strategic Award (084344), the US National Institutes of Health (AI017892), and the UK Medical Research Council (G0901682).
dc.languageEnglishen
dc.language.isoenen
dc.publisherNational Academy of Sciences
dc.subjectUgandaen
dc.subjectPre-Eclampsiaen
dc.subjectNK cellsen
dc.subjectMaternal mortalityen
dc.subjectKIRen
dc.titleA KIR B centromeric region present in Africans but not Europeans protects pregnant women from pre-eclampsiaen
dc.typeArticle
dc.description.versionThis is the accepted manuscript of a paper published in PNAS (A Nakimuli, O Chazara, SE Hiby, L Farrell, S Tukwasibwe, J Jayaraman, JA Traherne, J Trowsdale, F Colucci, Emma Lougee, RW Vaughan, AM Elliott, J Byamugishaa, P Kaleebu, F Mirembe, N Nemat-Gorgani, P Parham, PJ Norman, A Moffett, PNAS 2015, 112, 845-850)en
prism.endingPage850
prism.publicationDate2015en
prism.publicationNamePNASen
prism.startingPage845
prism.volume112en
dc.rioxxterms.funderWellcome Trust
dc.rioxxterms.funderBritish Heart Foundation
dc.rioxxterms.funderNational Institutes of Health
dc.rioxxterms.funderMedical Research Council
dc.rioxxterms.projectid090108/Z/09/Z
dc.rioxxterms.projectid085992/Z/08/Z
dc.rioxxterms.projectid089821/Z/09/Z
dc.rioxxterms.projectid084344
dc.rioxxterms.projectidPG/ 09/077/27964
dc.rioxxterms.projectidAI017892
dc.rioxxterms.projectidG0901682
rioxxterms.versionofrecord10.1073/pnas.1413453112en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2015-01-05en
dc.contributor.orcidTraherne, James [0000-0002-6003-8559]
dc.contributor.orcidTrowsdale, John [0000-0002-0150-5698]
dc.contributor.orcidColucci, Francesco [0000-0001-5193-6376]
dc.contributor.orcidMoffett, Ashley [0000-0002-8388-9073]
dc.identifier.eissn1091-6490
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idWellcome Trust (085992/Z/08/Z)
pubs.funder-project-idWellcome Trust (090108/Z/09/Z)
pubs.funder-project-idBritish Heart Foundation (PG/09/077/27964)
pubs.funder-project-idWellcome Trust (089821/Z/09/Z)
pubs.funder-project-idMRC (G0901682)
pubs.funder-project-idWellcome Trust (100140/Z/12/Z)
pubs.funder-project-idWellcome Trust (100891/Z/13/Z)
rioxxterms.freetoread.startdate2015-07-05


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record