Polymorphisms in genes of interleukin 12 and its receptors and their association with protection against severe malarial anaemia in children in western Kenya
Abstract Background Malarial anaemia is characterized by destruction of malaria infected red blood cells and suppression of erythropoiesis. Interleukin 12 (IL12) significantly boosts erythropoietic responses in murine models of malarial anaemia and decreased IL12 levels are associated with severe ma...
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ftdoajarticles:oai:doaj.org/article:8592fb41621e4fbdb21682494c0a1d91 2023-05-15T15:12:31+02:00 Polymorphisms in genes of interleukin 12 and its receptors and their association with protection against severe malarial anaemia in children in western Kenya Slutsker Laurence Lal Altaf A Terlouw Dianne Nahlen Bernard Kariuki Simon ter Kuile Feiko Crawford Sara Eng Jodi Prather Donald Zhang Lyna Udhayakumar Venkatachalam Shi Ya 2010-03-01T00:00:00Z https://doi.org/10.1186/1475-2875-9-87 https://doaj.org/article/8592fb41621e4fbdb21682494c0a1d91 EN eng BMC http://www.malariajournal.com/content/9/1/87 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-9-87 1475-2875 https://doaj.org/article/8592fb41621e4fbdb21682494c0a1d91 Malaria Journal, Vol 9, Iss 1, p 87 (2010) Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2010 ftdoajarticles https://doi.org/10.1186/1475-2875-9-87 2023-01-08T01:36:01Z Abstract Background Malarial anaemia is characterized by destruction of malaria infected red blood cells and suppression of erythropoiesis. Interleukin 12 (IL12) significantly boosts erythropoietic responses in murine models of malarial anaemia and decreased IL12 levels are associated with severe malarial anaemia (SMA) in children. Based on the biological relevance of IL12 in malaria anaemia, the relationship between genetic polymorphisms of IL12 and its receptors and SMA was examined. Methods Fifty-five tagging single nucleotide polymorphisms covering genes encoding two IL12 subunits, IL12A and IL12B , and its receptors, IL12RB1 and IL12RB2 , were examined in a cohort of 913 children residing in Asembo Bay region of western Kenya. Results An increasing copy number of minor variant (C) in IL12A (rs2243140) was significantly associated with a decreased risk of SMA ( P = 0.006; risk ratio, 0.52 for carrying one copy of allele C and 0.28 for two copies). Individuals possessing two copies of a rare variant (C) in IL12RB1 (rs429774) also appeared to be strongly protective against SMA ( P = 0.00005; risk ratio, 0.18). In addition, children homozygous for another rare allele (T) in IL12A (rs22431348) were associated with reduced risk of severe anaemia (SA) ( P = 0.004; risk ratio, 0.69) and of severe anaemia with any parasitaemia (SAP) ( P = 0.004; risk ratio, 0.66). In contrast, AG genotype for another variant in IL12RB1 (rs383483) was associated with susceptibility to high-density parasitaemia (HDP) ( P = 0.003; risk ratio, 1.21). Conclusions This study has shown strong associations between polymorphisms in the genes of IL12A and IL12RB1 and protection from SMA in Kenyan children, suggesting that human genetic variants of IL12 related genes may significantly contribute to the development of anaemia in malaria patients. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 9 1 |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
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Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Slutsker Laurence Lal Altaf A Terlouw Dianne Nahlen Bernard Kariuki Simon ter Kuile Feiko Crawford Sara Eng Jodi Prather Donald Zhang Lyna Udhayakumar Venkatachalam Shi Ya Polymorphisms in genes of interleukin 12 and its receptors and their association with protection against severe malarial anaemia in children in western Kenya |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background Malarial anaemia is characterized by destruction of malaria infected red blood cells and suppression of erythropoiesis. Interleukin 12 (IL12) significantly boosts erythropoietic responses in murine models of malarial anaemia and decreased IL12 levels are associated with severe malarial anaemia (SMA) in children. Based on the biological relevance of IL12 in malaria anaemia, the relationship between genetic polymorphisms of IL12 and its receptors and SMA was examined. Methods Fifty-five tagging single nucleotide polymorphisms covering genes encoding two IL12 subunits, IL12A and IL12B , and its receptors, IL12RB1 and IL12RB2 , were examined in a cohort of 913 children residing in Asembo Bay region of western Kenya. Results An increasing copy number of minor variant (C) in IL12A (rs2243140) was significantly associated with a decreased risk of SMA ( P = 0.006; risk ratio, 0.52 for carrying one copy of allele C and 0.28 for two copies). Individuals possessing two copies of a rare variant (C) in IL12RB1 (rs429774) also appeared to be strongly protective against SMA ( P = 0.00005; risk ratio, 0.18). In addition, children homozygous for another rare allele (T) in IL12A (rs22431348) were associated with reduced risk of severe anaemia (SA) ( P = 0.004; risk ratio, 0.69) and of severe anaemia with any parasitaemia (SAP) ( P = 0.004; risk ratio, 0.66). In contrast, AG genotype for another variant in IL12RB1 (rs383483) was associated with susceptibility to high-density parasitaemia (HDP) ( P = 0.003; risk ratio, 1.21). Conclusions This study has shown strong associations between polymorphisms in the genes of IL12A and IL12RB1 and protection from SMA in Kenyan children, suggesting that human genetic variants of IL12 related genes may significantly contribute to the development of anaemia in malaria patients. |
format |
Article in Journal/Newspaper |
author |
Slutsker Laurence Lal Altaf A Terlouw Dianne Nahlen Bernard Kariuki Simon ter Kuile Feiko Crawford Sara Eng Jodi Prather Donald Zhang Lyna Udhayakumar Venkatachalam Shi Ya |
author_facet |
Slutsker Laurence Lal Altaf A Terlouw Dianne Nahlen Bernard Kariuki Simon ter Kuile Feiko Crawford Sara Eng Jodi Prather Donald Zhang Lyna Udhayakumar Venkatachalam Shi Ya |
author_sort |
Slutsker Laurence |
title |
Polymorphisms in genes of interleukin 12 and its receptors and their association with protection against severe malarial anaemia in children in western Kenya |
title_short |
Polymorphisms in genes of interleukin 12 and its receptors and their association with protection against severe malarial anaemia in children in western Kenya |
title_full |
Polymorphisms in genes of interleukin 12 and its receptors and their association with protection against severe malarial anaemia in children in western Kenya |
title_fullStr |
Polymorphisms in genes of interleukin 12 and its receptors and their association with protection against severe malarial anaemia in children in western Kenya |
title_full_unstemmed |
Polymorphisms in genes of interleukin 12 and its receptors and their association with protection against severe malarial anaemia in children in western Kenya |
title_sort |
polymorphisms in genes of interleukin 12 and its receptors and their association with protection against severe malarial anaemia in children in western kenya |
publisher |
BMC |
publishDate |
2010 |
url |
https://doi.org/10.1186/1475-2875-9-87 https://doaj.org/article/8592fb41621e4fbdb21682494c0a1d91 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 9, Iss 1, p 87 (2010) |
op_relation |
http://www.malariajournal.com/content/9/1/87 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-9-87 1475-2875 https://doaj.org/article/8592fb41621e4fbdb21682494c0a1d91 |
op_doi |
https://doi.org/10.1186/1475-2875-9-87 |
container_title |
Malaria Journal |
container_volume |
9 |
container_issue |
1 |
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1766343193370034176 |