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Open Access 01-12-2010 | Research

Polymorphisms in genes of interleukin 12 and its receptors and their association with protection against severe malarial anaemia in children in western Kenya

Authors: Lyna Zhang, Donald Prather, Jodi Vanden Eng, Sara Crawford, Simon Kariuki, Feiko ter Kuile, Dianne Terlouw, Bernard Nahlen, Altaf A Lal, Laurence Slutsker, Venkatachalam Udhayakumar, Ya Ping Shi

Published in: Malaria Journal | Issue 1/2010

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.

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Title: Polymorphisms in genes of interleukin 12 and its receptors and their association with protection against severe malarial anaemia in children in western Kenya
Authors: Lyna Zhang
Donald Prather
Jodi Vanden Eng
Sara Crawford
Simon Kariuki
Feiko ter Kuile
Dianne Terlouw
Bernard Nahlen
Altaf A Lal
Laurence Slutsker
Venkatachalam Udhayakumar
Ya Ping Shi
Publication date: 01-12-2010
Publisher: BioMed Central
Published in: Malaria Journal / Issue 1/2010
Electronic ISSN: 1475-2875
DOI: https://doi.org/10.1186/1475-2875-9-87

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Conclusions

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