期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 112, 期 3, 页码 845-850出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1413453112
关键词
Uganda; pre-eclampsia; NK cells; maternal mortality; KIR
资金
- Wellcome Trust [090108/Z/09/Z, 085992/Z/08/Z, 089821/Z/09/Z, 084344]
- British Heart Foundation [PG/09/077/27964]
- Centre for Trophoblast Research at the University of Cambridge
- Wellcome Trust Uganda PhD Fellowship in Infection and Immunity
- National Institutes of Health [AI090905]
- United Kingdom Medical Research Council [G0901682]
- Wellcome Trust [085992/Z/08/Z, 090108/Z/09/Z, 089821/Z/09/Z] Funding Source: Wellcome Trust
- British Heart Foundation [PG/09/077/27964] Funding Source: researchfish
- Medical Research Council [G0901682] Funding Source: researchfish
- MRC [G0901682] Funding Source: UKRI
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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