Diversity of KIR genes and their HLA-C ligands in Ugandan populations with historically varied malaria transmission intensity
Abstract Background Malaria 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 likel...
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| Format: | Article |
| Language: | English |
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BMC
2021-02-01
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| Series: | Malaria Journal |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12936-021-03652-y |
| _version_ | 1818617304912494592 |
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| author | Stephen Tukwasibwe James A. Traherne Olympe Chazara Jyothi Jayaraman John Trowsdale Ashley Moffett Wei Jiang Joaniter I. Nankabirwa John Rek Emmanuel Arinaitwe Samuel L. Nsobya Maxine Atuheirwe Mubiru Frank Anguzu Godwin Prasanna Jagannathan Stephen Cose Moses R. Kamya Grant Dorsey Philip J. Rosenthal Francesco Colucci Annettee Nakimuli |
| author_facet | Stephen Tukwasibwe James A. Traherne Olympe Chazara Jyothi Jayaraman John Trowsdale Ashley Moffett Wei Jiang Joaniter I. Nankabirwa John Rek Emmanuel Arinaitwe Samuel L. Nsobya Maxine Atuheirwe Mubiru Frank Anguzu Godwin Prasanna Jagannathan Stephen Cose Moses R. Kamya Grant Dorsey Philip J. Rosenthal Francesco Colucci Annettee Nakimuli |
| author_sort | Stephen Tukwasibwe |
| collection | DOAJ |
| description | Abstract Background Malaria 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. Methods High 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. Results The 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. Conclusions The 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. |
| first_indexed | 2024-12-16T17:03:35Z |
| format | Article |
| id | doaj.art-43d22a087802415eb09d389bde9ea02e |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-12-16T17:03:35Z |
| publishDate | 2021-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj.art-43d22a087802415eb09d389bde9ea02e2022-12-21T22:23:39ZengBMCMalaria Journal1475-28752021-02-0120111110.1186/s12936-021-03652-yDiversity of KIR genes and their HLA-C ligands in Ugandan populations with historically varied malaria transmission intensityStephen Tukwasibwe0James A. Traherne1Olympe Chazara2Jyothi Jayaraman3John Trowsdale4Ashley Moffett5Wei Jiang6Joaniter I. Nankabirwa7John Rek8Emmanuel Arinaitwe9Samuel L. Nsobya10Maxine Atuheirwe11Mubiru Frank12Anguzu Godwin13Prasanna Jagannathan14Stephen Cose15Moses R. Kamya16Grant Dorsey17Philip J. Rosenthal18Francesco Colucci19Annettee Nakimuli20Department of Obstetrics and Gynaecology, School of Medicine, Makerere University College of Health SciencesDepartment of Pathology, University of CambridgeDepartment of Pathology, University of CambridgeDepartment of Pathology, University of CambridgeDepartment of Pathology, University of CambridgeDepartment of Pathology, University of CambridgeDepartment of Pathology, University of CambridgeDepartment of Obstetrics and Gynaecology, School of Medicine, Makerere University College of Health SciencesInfectious Diseases Research CollaborationInfectious Diseases Research CollaborationDepartment of Obstetrics and Gynaecology, School of Medicine, Makerere University College of Health SciencesDepartment of Obstetrics and Gynaecology, School of Medicine, Makerere University College of Health SciencesDepartment of Obstetrics and Gynaecology, School of Medicine, Makerere University College of Health SciencesDepartment of Obstetrics and Gynaecology, School of Medicine, Makerere University College of Health SciencesStanford University, School of MedicineMRC/UVRI and LSHTM Uganda Research UnitDepartment of Obstetrics and Gynaecology, School of Medicine, Makerere University College of Health SciencesUniversity of CaliforniaUniversity of CaliforniaUniversity of Cambridge Centre for Trophoblast ResearchDepartment of Obstetrics and Gynaecology, School of Medicine, Makerere University College of Health SciencesAbstract Background Malaria 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. Methods High 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. Results The 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. Conclusions The 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.https://doi.org/10.1186/s12936-021-03652-yGenetic diversityHuman leukocyte antigenKiller-cell immunoglobulin-like receptorMalariaUganda |
| spellingShingle | Stephen Tukwasibwe James A. Traherne Olympe Chazara Jyothi Jayaraman John Trowsdale Ashley Moffett Wei Jiang Joaniter I. Nankabirwa John Rek Emmanuel Arinaitwe Samuel L. Nsobya Maxine Atuheirwe Mubiru Frank Anguzu Godwin Prasanna Jagannathan Stephen Cose Moses R. Kamya Grant Dorsey Philip J. Rosenthal Francesco Colucci Annettee Nakimuli Diversity of KIR genes and their HLA-C ligands in Ugandan populations with historically varied malaria transmission intensity Malaria Journal Genetic diversity Human leukocyte antigen Killer-cell immunoglobulin-like receptor Malaria Uganda |
| title | Diversity of KIR genes and their HLA-C ligands in Ugandan populations with historically varied malaria transmission intensity |
| title_full | Diversity of KIR genes and their HLA-C ligands in Ugandan populations with historically varied malaria transmission intensity |
| title_fullStr | Diversity of KIR genes and their HLA-C ligands in Ugandan populations with historically varied malaria transmission intensity |
| title_full_unstemmed | Diversity of KIR genes and their HLA-C ligands in Ugandan populations with historically varied malaria transmission intensity |
| title_short | Diversity of KIR genes and their HLA-C ligands in Ugandan populations with historically varied malaria transmission intensity |
| title_sort | diversity of kir genes and their hla c ligands in ugandan populations with historically varied malaria transmission intensity |
| topic | Genetic diversity Human leukocyte antigen Killer-cell immunoglobulin-like receptor Malaria Uganda |
| url | https://doi.org/10.1186/s12936-021-03652-y |
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