ArticleProceedings of the National Academy of Sciences of the United States of America2015
A KIR B centromeric region present in Africans but not Europeans protects pregnant women from pre-eclampsia.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 3 of them syntheses that pooled it.
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Who cites it
93 citing papers in PubMed, 3 syntheses or guidelines pooled it, 148 citations in OpenAlex.
- Preeclampsia Genomic Susceptibility Factors in Populations of African Ancestry: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2026Pooled it
- The CD94/NKG2A inhibitory receptor educates uterine NK cells to optimize pregnancy outcomes in humans and mice.Immunity · 2021Pooled it
- The Roles of Uterine Natural Killer (NK) Cells and KIR/HLA-C Combination in the Development of Preeclampsia: A Systematic Review.BioMed research international · 2020Pooled it
- Immunology of Normal Pregnancy and Preeclampsia and the Role of Placental Non-Classical HLA and Decidual NK Cells.International journal of molecular sciences · 2026Review
- Natural Killer Cell Assays: Clinical Applications and Future Directions.Annals of laboratory medicine · 2026Review
- Challenges and Prospects in Managing Hypertensive Disorders of Pregnancy in Sub-Saharan Africa: A Narrative Review.International journal of women's health · 2026Review
- Genetic factors in the risk assessment of preeclampsia: a review of recent findings.Molecular biology reports · 2025Review
- Bridging the Gap: The Challenge of Conducting Clinical Trials in Sub-Saharan Africa.Anesthesia and analgesia · 2025Article
- Review
- The Role of Killer Ig-like Receptors in Diseases from A to Z.International journal of molecular sciences · 2025Review
- Peptide-specific natural killer cell receptors.Oxford open immunology · 2025Review
- Cervical EVT isolation for non-invasive fetal HLA typing in early pregnancy is limited by purity and maternal cell contamination; a methodological comparison.Frontiers in immunology · 2025Article
- Inhibitory KIRs decrease HLA class II-mediated protection in Type 1 Diabetes.PLoS genetics · 2024Article
- Global inequities in adverse pregnancy outcomes: what can we do?AJOG global reports · 2024Article
- Combined maternal KIR2DL4 and fetal HLA-G polymorphisms were associated with preeclampsia in a Han Chinese population.Frontiers in genetics · 2024Article
- Local immune recognition of trophoblast in early human pregnancy: controversies and questions.Nature reviews. Immunology · 2023Review
- No association of a Vascular endothelial growth factor A (VEGFA) gene polymorphism with pre-eclampsia among pregnant women in Uganda.BMC genomics · 2023Article
- The central role of natural killer cells in preeclampsia.Frontiers in immunology · 2023Review
- Editorial: A century of health professions' education, training, academic research and service at Makerere University, Kampala, Uganda.African health sciences · 2022Article
- Characterization of KIRHLA · 2022Article
33 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 6 institutions in 3 countries.
Funding
Abstract
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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