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

Zang, Lyna, Prather, Donald, Vanden, Jodi, Crawford, Sara, Kariuki, Simon, terKuile, Feiko ORCID: https://orcid.org/0000-0003-3663-5617, Terlouw, Anja ORCID: https://orcid.org/0000-0001-5327-8995, Nahlen, Bernard, Lal, Altaf A., Slutsker, Laurence, Udhayakumar, Venkatachalam and Shi, Ya Ping (2010) '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, Vol 9, Issue 87.

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Abstract

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.

Item Type:	Article
Additional Information:	The definitive version of this article is available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2858737/
Subjects:	QU Biochemistry > Genetics > QU 500 Genetic phenomena WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria WS Pediatrics > Diseases of Children and Adolescents > General Diseases > WS 200 General works
Digital Object Identifer (DOI):	https://doi.org/10.1186/1475-2875-9-87
Depositing User:	Helen Wong
Date Deposited:	11 Aug 2010 09:49
Last Modified:	16 Dec 2020 11:11
URI:	https://archive.lstmed.ac.uk/id/eprint/1106

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