A KIR B centromeric region present in Africans but not Europeans protects pregnant women from pre-eclampsia

Nakimuli Annettee; Chazara Olympe; Hiby Susan E.Farrell LydiaTukwasibwe StephenJayaraman JyothiTraherne James A.Trowsdale JohnColucci FrancescoLougee EmmaVaughan Robert W.Elliott Alison M.Byamugisha JosaphatKaleebu PontianoMirembe FlorenceNemat-Gorgani NedaParham PeterNorman Paul J.Moffett Ashley

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A KIR B centromeric region present in Africans but not Europeans protects pregnant women from pre-eclampsia

机译：A KIR B centromeric region present in Africans but not Europeans protects pregnant women from pre-eclampsia

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In sub-Saharan Africans, maternal mortality is unacceptably high, with >400 deaths per 100,000 births compared with <10 deaths per 100,000 births in Europeans. One-third of the deaths are caused by pre-eclampsia, a syndrome arising from defective placentation. Controlling placentation are maternal natural killer (NK) cells that use killer-cell immunoglobulin-like receptor (KIR) to recognize the fetal HLA-C molecules on invading trophoblast. We analyzed genetic polymorphisms of maternal KIR and fetal HLA-C in 484 normal and 254 pre-eclamptic pregnancies at Mulago Hospital, Kampala, Uganda. The combination of maternal KIR AA genotypes and fetal HLA-C alleles encoding the C2 epitope associates with pre-eclampsia P = 0.0318, odds ratio (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.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2015年第3期|845-850|共6页
作者
Nakimuli Annettee; Chazara Olympe; Hiby Susan E.Farrell LydiaTukwasibwe StephenJayaraman JyothiTraherne James A.Trowsdale JohnColucci FrancescoLougee EmmaVaughan Robert W.Elliott Alison M.Byamugisha JosaphatKaleebu PontianoMirembe FlorenceNemat-Gorgani NedaParham PeterNorman Paul J.Moffett Ashley;
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作者单位

Makerere Univ, Dept Obstet & Gynaecol, Kampala, Uganda;

Stanford Univ, Dept Biol Struct, Stanford, CA 94305 USA;

Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, EnglandUniv London London Sch Hyg & Trop Med, Dept Clin Res, London WC1E 7HT, EnglandUganda Virus Res Inst, Uganda Res Unit AIDS, MRC, Entebbe, UgandaUniv Cambridge, Cambridge Inst Med Res, Cambridge CB2 0XY, EnglandUniv Cambridge, Dept Pathol, Div Immunol, Cambridge CB2 1QP, EnglandUniv Cambridge, Ctr Trophoblast Res, Dept Obstet & Gynaecol, Cambridge CB2 0WS, EnglandGuys Hosp, Clin Transplantat Lab, Viapath, London SE1 9RT, England;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
Uganda; pre-eclampsia; NK cells; maternal mortality; KIR;

A KIR B centromeric region present in Africans but not Europeans protects pregnant women from pre-eclampsia

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