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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Polymorphisms in genes of interleukin 12 and its receptors and their association with protection against severe malarial anaemia in children in western Kenya
Malaria Journal, Volume 9, No. 1, Article 87, Year 2010
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Description
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. © 2010 Zhang et al; licensee BioMed Central Ltd.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC2858737/bin/1475-2875-9-87-S1.XLS
Authors & Co-Authors
Zhang, L.
United States, Atlanta
National Center for Emerging and Zoonotic Infectious Diseases
United States, Atlanta
Coordinating Center for Health Promotion
Prather, Donald
United States, Atlanta
National Center for Emerging and Zoonotic Infectious Diseases
Vanden Eng, Jodi Leigh
United States, Atlanta
National Center for Emerging and Zoonotic Infectious Diseases
Crawford, Sara B.
United States, Atlanta
National Center for Emerging and Zoonotic Infectious Diseases
Kariuki, Simon K.
Kenya, Nairobi
Kenya Medical Research Institute
ter Kuile, Feiko O.
United Kingdom, Liverpool
Liverpool School of Tropical Medicine
Terlouw, Dianne Janette
United Kingdom, Liverpool
Liverpool School of Tropical Medicine
Nahlen, Bernard L.
United States, Atlanta
National Center for Emerging and Zoonotic Infectious Diseases
Lal, Altaf A.
United States, Atlanta
National Center for Emerging and Zoonotic Infectious Diseases
Slutsker, Laurence
United States, Atlanta
National Center for Emerging and Zoonotic Infectious Diseases
Udhayakumar, Venkatachalam
United States, Atlanta
National Center for Emerging and Zoonotic Infectious Diseases
Shi, Yaping
United States, Atlanta
National Center for Emerging and Zoonotic Infectious Diseases
Statistics
Citations: 36
Authors: 12
Affiliations: 4
Identifiers
Doi:
10.1186/1475-2875-9-87
e-ISSN:
14752875
Research Areas
Genetics And Genomics
Infectious Diseases
Maternal And Child Health
Study Design
Cohort Study
Study Locations
Kenya