ArticleMalaria journal2010
Polymorphisms in genes of interleukin 12 and its receptors and their association with protection against severe malarial anaemia in children in western Kenya.
Article in Malaria journal, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 32 citations in OpenAlex.
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- Cerebral Malaria: Current Clinical and Immunological Aspects.Frontiers in immunology · 2022Review
- Human genetics and malaria resistance.Human genetics · 2020Review
- Genetics of Malaria Inflammatory Responses: A Pathogenesis Perspective.Frontiers in immunology · 2019Review
- Novel genetic polymorphisms associated with severe malaria and under selective pressure in North-eastern Tanzania.PLoS genetics · 2018Article
- Environmental Correlation Analysis for Genes Associated with Protection against Malaria.Molecular biology and evolution · 2016Article
- IL12Rβ1: the cytokine receptor that we used to know.Cytokine · 2015Review
- IL-12Rβ1 deficiency: mutation update and description of the IL12RB1 variation database.Human mutation · 2013Review
- IL1B, IL4R, IL12RB1 and TNF gene polymorphisms are associated with Plasmodium vivax malaria in Brazil.Malaria journal · 2012Article
- The host genetic diversity in malaria infection.Journal of tropical medicine · 2012Article
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- Gene expression profiling of dendritic cells reveals important mechanisms associated with predisposition to Staphylococcus infections.PloS one · 2011Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMalarial 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.
methodsFifty-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.
resultsAn 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).
conclusionsThis 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.
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