Genetic variation in CSF2 (5q31.1) is associated with longitudinal susceptibility to pediatric malaria, severe malarial anemia, and all-cause mortality in a high-burden malaria and HIV region of Kenya
Abstract Plasmodium falciparum infections remain among the leading causes of morbidity and mortality in holoendemic transmission areas. Located within region 5q31.1, the colony-stimulating factor 2 gene (CSF2) encodes granulocyte–macrophage colony-stimulating factor (GM-CSF), a hematopoietic growth...
Published in: | Tropical Medicine and Health |
---|---|
Main Authors: | , , , , , , , , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
BMC
2022
|
Subjects: | |
Online Access: | https://doi.org/10.1186/s41182-022-00432-5 https://doaj.org/article/9181a3a765424ab5950663800c7efad4 |
id |
ftdoajarticles:oai:doaj.org/article:9181a3a765424ab5950663800c7efad4 |
---|---|
record_format |
openpolar |
spelling |
ftdoajarticles:oai:doaj.org/article:9181a3a765424ab5950663800c7efad4 2023-05-15T15:15:30+02:00 Genetic variation in CSF2 (5q31.1) is associated with longitudinal susceptibility to pediatric malaria, severe malarial anemia, and all-cause mortality in a high-burden malaria and HIV region of Kenya Lily E. Kisia Qiuying Cheng Evans Raballah Elly O. Munde Benjamin H. McMahon Nick W. Hengartner John M. Ong’echa Kiprotich Chelimo Christophe G. Lambert Collins Ouma Prakasha Kempaiah Douglas J. Perkins Kristan A. Schneider Samuel B. Anyona 2022-06-01T00:00:00Z https://doi.org/10.1186/s41182-022-00432-5 https://doaj.org/article/9181a3a765424ab5950663800c7efad4 EN eng BMC https://doi.org/10.1186/s41182-022-00432-5 https://doaj.org/toc/1349-4147 doi:10.1186/s41182-022-00432-5 1349-4147 https://doaj.org/article/9181a3a765424ab5950663800c7efad4 Tropical Medicine and Health, Vol 50, Iss 1, Pp 1-15 (2022) P. falciparum CSF2 GM-CSF Malaria Genotypes Haplotypes Arctic medicine. Tropical medicine RC955-962 article 2022 ftdoajarticles https://doi.org/10.1186/s41182-022-00432-5 2022-12-30T21:23:10Z Abstract Plasmodium falciparum infections remain among the leading causes of morbidity and mortality in holoendemic transmission areas. Located within region 5q31.1, the colony-stimulating factor 2 gene (CSF2) encodes granulocyte–macrophage colony-stimulating factor (GM-CSF), a hematopoietic growth factor that mediates host immune responses. Since the effect of CSF2 variation on malaria pathogenesis remains unreported, we investigated the impact of two genetic variants in the 5q31.1 gene region flanking CSF2:g-7032 G > A (rs168681:G > A) and CSF2:g.64544T > C (rs246835:T > C) on the rate and timing of malaria and severe malarial anemia (SMA, Hb < 5.0 g/dL) episodes over 36 months of follow-up. Children (n = 1654, aged 2–70 months) were recruited from a holoendemic P. falciparum transmission area of western Kenya. Decreased incidence rate ratio (IRR) for malaria was conferred by inheritance of the CSF2:g.64544 TC genotype (P = 0.0277) and CSF2 AC/GC diplotype (P = 0.0015). Increased IRR for malaria was observed in carriers of the CSF2 AT/GC diplotype (P = 0.0237), while the inheritance of the CSF2 AT haplotype increased the IRR for SMA (P = 0.0166). A model estimating the longitudinal risk of malaria showed decreased hazard rates among CSF2 AC haplotype carriers (P = 0.0045). Investigation of all-cause mortality revealed that inheritance of the GA genotype at CSF2:g-7032 increased the risk of mortality (P = 0.0315). Higher risk of SMA and all-cause mortality were observed in younger children (P < 0.0001 and P = 0.0015), HIV-1(+) individuals (P < 0.0001 and P < 0.0001), and carriers of HbSS (P = 0.0342 and P = 0.0019). Results from this holoendemic P. falciparum area show that variation in gene region 5q31.1 influences susceptibility to malaria, SMA, and mortality, as does age, HIV-1 status, and inheritance of HbSS. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Tropical Medicine and Health 50 1 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
P. falciparum CSF2 GM-CSF Malaria Genotypes Haplotypes Arctic medicine. Tropical medicine RC955-962 |
spellingShingle |
P. falciparum CSF2 GM-CSF Malaria Genotypes Haplotypes Arctic medicine. Tropical medicine RC955-962 Lily E. Kisia Qiuying Cheng Evans Raballah Elly O. Munde Benjamin H. McMahon Nick W. Hengartner John M. Ong’echa Kiprotich Chelimo Christophe G. Lambert Collins Ouma Prakasha Kempaiah Douglas J. Perkins Kristan A. Schneider Samuel B. Anyona Genetic variation in CSF2 (5q31.1) is associated with longitudinal susceptibility to pediatric malaria, severe malarial anemia, and all-cause mortality in a high-burden malaria and HIV region of Kenya |
topic_facet |
P. falciparum CSF2 GM-CSF Malaria Genotypes Haplotypes Arctic medicine. Tropical medicine RC955-962 |
description |
Abstract Plasmodium falciparum infections remain among the leading causes of morbidity and mortality in holoendemic transmission areas. Located within region 5q31.1, the colony-stimulating factor 2 gene (CSF2) encodes granulocyte–macrophage colony-stimulating factor (GM-CSF), a hematopoietic growth factor that mediates host immune responses. Since the effect of CSF2 variation on malaria pathogenesis remains unreported, we investigated the impact of two genetic variants in the 5q31.1 gene region flanking CSF2:g-7032 G > A (rs168681:G > A) and CSF2:g.64544T > C (rs246835:T > C) on the rate and timing of malaria and severe malarial anemia (SMA, Hb < 5.0 g/dL) episodes over 36 months of follow-up. Children (n = 1654, aged 2–70 months) were recruited from a holoendemic P. falciparum transmission area of western Kenya. Decreased incidence rate ratio (IRR) for malaria was conferred by inheritance of the CSF2:g.64544 TC genotype (P = 0.0277) and CSF2 AC/GC diplotype (P = 0.0015). Increased IRR for malaria was observed in carriers of the CSF2 AT/GC diplotype (P = 0.0237), while the inheritance of the CSF2 AT haplotype increased the IRR for SMA (P = 0.0166). A model estimating the longitudinal risk of malaria showed decreased hazard rates among CSF2 AC haplotype carriers (P = 0.0045). Investigation of all-cause mortality revealed that inheritance of the GA genotype at CSF2:g-7032 increased the risk of mortality (P = 0.0315). Higher risk of SMA and all-cause mortality were observed in younger children (P < 0.0001 and P = 0.0015), HIV-1(+) individuals (P < 0.0001 and P < 0.0001), and carriers of HbSS (P = 0.0342 and P = 0.0019). Results from this holoendemic P. falciparum area show that variation in gene region 5q31.1 influences susceptibility to malaria, SMA, and mortality, as does age, HIV-1 status, and inheritance of HbSS. |
format |
Article in Journal/Newspaper |
author |
Lily E. Kisia Qiuying Cheng Evans Raballah Elly O. Munde Benjamin H. McMahon Nick W. Hengartner John M. Ong’echa Kiprotich Chelimo Christophe G. Lambert Collins Ouma Prakasha Kempaiah Douglas J. Perkins Kristan A. Schneider Samuel B. Anyona |
author_facet |
Lily E. Kisia Qiuying Cheng Evans Raballah Elly O. Munde Benjamin H. McMahon Nick W. Hengartner John M. Ong’echa Kiprotich Chelimo Christophe G. Lambert Collins Ouma Prakasha Kempaiah Douglas J. Perkins Kristan A. Schneider Samuel B. Anyona |
author_sort |
Lily E. Kisia |
title |
Genetic variation in CSF2 (5q31.1) is associated with longitudinal susceptibility to pediatric malaria, severe malarial anemia, and all-cause mortality in a high-burden malaria and HIV region of Kenya |
title_short |
Genetic variation in CSF2 (5q31.1) is associated with longitudinal susceptibility to pediatric malaria, severe malarial anemia, and all-cause mortality in a high-burden malaria and HIV region of Kenya |
title_full |
Genetic variation in CSF2 (5q31.1) is associated with longitudinal susceptibility to pediatric malaria, severe malarial anemia, and all-cause mortality in a high-burden malaria and HIV region of Kenya |
title_fullStr |
Genetic variation in CSF2 (5q31.1) is associated with longitudinal susceptibility to pediatric malaria, severe malarial anemia, and all-cause mortality in a high-burden malaria and HIV region of Kenya |
title_full_unstemmed |
Genetic variation in CSF2 (5q31.1) is associated with longitudinal susceptibility to pediatric malaria, severe malarial anemia, and all-cause mortality in a high-burden malaria and HIV region of Kenya |
title_sort |
genetic variation in csf2 (5q31.1) is associated with longitudinal susceptibility to pediatric malaria, severe malarial anemia, and all-cause mortality in a high-burden malaria and hiv region of kenya |
publisher |
BMC |
publishDate |
2022 |
url |
https://doi.org/10.1186/s41182-022-00432-5 https://doaj.org/article/9181a3a765424ab5950663800c7efad4 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Tropical Medicine and Health, Vol 50, Iss 1, Pp 1-15 (2022) |
op_relation |
https://doi.org/10.1186/s41182-022-00432-5 https://doaj.org/toc/1349-4147 doi:10.1186/s41182-022-00432-5 1349-4147 https://doaj.org/article/9181a3a765424ab5950663800c7efad4 |
op_doi |
https://doi.org/10.1186/s41182-022-00432-5 |
container_title |
Tropical Medicine and Health |
container_volume |
50 |
container_issue |
1 |
_version_ |
1766345873207328768 |