Evidence map›Paper›PMID 33632228›Full record

ArticleMalaria journal2021

Diversity of KIR genes and their HLA-C ligands in Ugandan populations with historically varied malaria transmission intensity.

Stephen Tukwasibwe, James A Traherne, Olympe Chazara, Jyothi Jayaraman, John Trowsdale, Ashley Moffett, Wei Jiang, Joaniter I Nankabirwa, John Rek, Emmanuel Arinaitwe and 11 more

Open access · goldAbstract read
In one paragraph

Article in Malaria journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.6field-weighted citation impact, top 38% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. The Role of Killer Ig-like Receptors in Diseases from A to Z.International journal of molecular sciences · 2025
    Review
  3. Article
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors at 6 institutions in 3 countries.

Stephen TukwasibweDepartment of Obstetrics and Gynaecology, School of Medicine, Makerere University College of Health Sciences, P.O BOX 7072, Kampala, Uganda.
James A TraherneDepartment of Pathology, University of Cambridge, Cambridge, UK.
Olympe ChazaraDepartment of Pathology, University of Cambridge, Cambridge, UK.
Jyothi JayaramanDepartment of Pathology, University of Cambridge, Cambridge, UK.
John TrowsdaleDepartment of Pathology, University of Cambridge, Cambridge, UK.
Ashley MoffettDepartment of Pathology, University of Cambridge, Cambridge, UK.
Wei JiangDepartment of Pathology, University of Cambridge, Cambridge, UK.
Joaniter I NankabirwaDepartment of Obstetrics and Gynaecology, School of Medicine, Makerere University College of Health Sciences, P.O BOX 7072, Kampala, Uganda.
John RekInfectious Diseases Research Collaboration, 2C Nakasero Hill Road, Kampala, Uganda.
Emmanuel ArinaitweInfectious Diseases Research Collaboration, 2C Nakasero Hill Road, Kampala, Uganda.
Samuel L NsobyaDepartment of Obstetrics and Gynaecology, School of Medicine, Makerere University College of Health Sciences, P.O BOX 7072, Kampala, Uganda.
Maxine AtuheirweDepartment of Obstetrics and Gynaecology, School of Medicine, Makerere University College of Health Sciences, P.O BOX 7072, Kampala, Uganda.
Mubiru FrankDepartment of Obstetrics and Gynaecology, School of Medicine, Makerere University College of Health Sciences, P.O BOX 7072, Kampala, Uganda.
Anguzu GodwinDepartment of Obstetrics and Gynaecology, School of Medicine, Makerere University College of Health Sciences, P.O BOX 7072, Kampala, Uganda.
Prasanna JagannathanStanford University, School of Medicine, Stanford, USA.
Stephen CoseMRC/UVRI and LSHTM Uganda Research Unit, Kampala, Uganda.
Moses R KamyaDepartment of Obstetrics and Gynaecology, School of Medicine, Makerere University College of Health Sciences, P.O BOX 7072, Kampala, Uganda.
Grant DorseyUniversity of California, San Francisco, USA.
Philip J RosenthalUniversity of California, San Francisco, USA.
Francesco ColucciUniversity of Cambridge Centre for Trophoblast Research, Cambridge, UK.
Annettee NakimuliDepartment of Obstetrics and Gynaecology, School of Medicine, Makerere University College of Health Sciences, P.O BOX 7072, Kampala, Uganda. annettee.nakimuli@gmail.com.ORCID http://orcid.org/0000-0003-2806-0243
University of Cambridge · GBInfectious Diseases Research Collaboration · UGMakerere University · UGUniversity of California, San Francisco · USStanford University · USUganda Virus Research Institute · UG

Funding

Transmission ProjectU19AI089674 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Joaniter Immaculate Nankabirwa · 2010 to 2026
$29.3M
University of California Launching Future Leaders in Global Health Research Training ProgramD43TW009343 · FIC · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CRAIG R COHEN, Sung-Jae Lee · 2017 to 2026
$14.7M
Resistance of Malaria Parasites to Artemisinin-Based TherapiesR01AI075045 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ROSENTHAL, PHILIP JON · 2009 to 2024
$8.4M
University of California Global Health Institute Program for Fellows and ScholarsR25TW009343 · FIC · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI COHEN, CRAIG R, STRATHDEE, STEFFANIE A. · 2012 to 2017
$6.4M
Training In Malaria Research in UgandaD43TW007375 · FIC · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ROSENTHAL, PHILIP JON · 2005 to 2019
$2.9M
Training in malaria surveillance, epidemiology and implementation science research to strengthen malaria policy and control in UgandaD43TW010526 · FIC · MAKERERE UNIVERSITY COLLEGE OF HEALTH SCIENCES · PI MATTHEW G DORSEY, MOSES Robert KAMYA · 2017 to 2026
$2.3M
Resistance of Malaria Parasites to Artemisinin-Based Combination TherapiesR56AI075045 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ROSENTHAL, PHILIP JON · 2008 to 2008
$618k
Impact of malaria control interventions on the infectious reservoir, host immunity, and drug resistance in UgandaK43TW010365 · FIC · INFECTIOUS DISEASES RES COLLABORATION · PI NANKABIRWA, JOANITER IMMACULATE · 2017 to 2021
$514k
European Research Council 695551FIC NIH HHS D43 TW007375FIC NIH HHS D43 TW009343FIC NIH HHS D43 TW010526FIC NIH HHS K43 TW010365FIC NIH HHS R25 TW009343NIAID NIH HHS R01 AI075045NIAID NIH HHS R56 AI075045NIAID NIH HHS U19 AI089674NIH HHS AI075045NIH HHS AI089674NIH HHS TW007375NIH HHS TW009343Wellcome Trust 200841/Z/16/Z
6 · The paper itself

Abstract

backgroundMalaria is one of the most serious infectious diseases in the world. The malaria burden is greatly affected by human immunity, and immune responses vary between populations. Genetic diversity in KIR and HLA-C genes, which are important in immunity to infectious diseases, is likely to play a role in this heterogeneity. Several studies have shown that KIR and HLA-C genes influence the immune response to viral infections, but few studies have examined the role of KIR and HLA-C in malaria infection, and these have used low-resolution genotyping. The aim of this study was to determine whether genetic variation in KIR and their HLA-C ligands differ in Ugandan populations with historically varied malaria transmission intensity using more comprehensive genotyping approaches.

methodsHigh throughput multiplex quantitative real-time PCR method was used to genotype KIR genetic variants and copy number variation and a high-throughput real-time PCR method was developed to genotype HLA-C1 and C2 allotypes for 1344 participants, aged 6 months to 10 years, enrolled from Ugandan populations with historically high (Tororo District), medium (Jinja District) and low (Kanungu District) malaria transmission intensity.

resultsThe prevalence of KIR3DS1, KIR2DL5, KIR2DS5, and KIR2DS1 genes was significantly lower in populations from Kanungu compared to Tororo (7.6 vs 13.2%: p = 0.006, 57.2 vs 66.4%: p = 0.005, 33.2 vs 46.6%: p < 0.001, and 19.7 vs 26.7%: p = 0.014, respectively) or Jinja (7.6 vs 18.1%: p < 0.001, 57.2 vs 63.8%: p = 0.048, 33.2 vs 43.5%: p = 0.002, and 19.7 vs 30.4%: p < 0.001, respectively). The prevalence of homozygous HLA-C2 was significantly higher in populations from Kanungu (31.6%) compared to Jinja (21.4%), p = 0.043, with no significant difference between Kanungu and Tororo (26.7%), p = 0.296.

conclusionsThe KIR3DS1, KIR2DL5, KIR2DS5 and KIR2DS1 genes may partly explain differences in transmission intensity of malaria since these genes have been positively selected for in places with historically high malaria transmission intensity. The high-throughput, multiplex, real-time HLA-C genotyping PCR method developed will be useful in disease-association studies involving large cohorts.

Indexed as

DNA Copy Number VariationsGenotypeChildChild, PreschoolHLA-C AntigensHumansInfantLigandsMalaria, FalciparumPotassium Channels, Inwardly RectifyingUgandaHLA-C AntigensLigandsPotassium Channels, Inwardly RectifyingGenetic diversityHuman leukocyte antigenKiller-cell immunoglobulin-like receptorMalariaUganda

Identifiers

PMID33632228
PMCPMC7908804
OpenAlexW3129045250

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.