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

Lyna Zhang; Donald Prather; Jodi Vanden Eng; Sara Crawford; Simon Kariuki; Feiko Ter Kuile; Anja Terlouw; Bernard Nahlen; Altaf A. Lal; Laurence Slutsker; Venkatachalam Udhayakumar; Ya Ping Shi

doi:10.1186/1475-2875-9-87

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

Lyna Zhang
, Donald Prather
, Jodi Vanden Eng
, Sara Crawford
, Simon Kariuki
, Feiko Ter Kuile
, Anja Terlouw
, Bernard Nahlen
, Altaf A. Lal
, Laurence Slutsker
, Venkatachalam Udhayakumar
, Ya Ping Shi

Clinical Sciences

Research output: Contribution to journal › Article › peer-review

24 Citations (Scopus)

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.

Original language	English
Article number	87
Journal	Malaria Journal
Volume	9
Issue number	1
DOIs	https://doi.org/10.1186/1475-2875-9-87
Publication status	Published - 29 Mar 2010

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Terlouw DJ 2010 Malaria JournalFinal published version, 951 KB

Cite this

Zhang, L., Prather, D., Eng, J. V., Crawford, S., Kariuki, S., Ter Kuile, F., Terlouw, A., Nahlen, B., Lal, A. A., Slutsker, L., Udhayakumar, V., & Shi, Y. P. (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, 9(1), Article 87. https://doi.org/10.1186/1475-2875-9-87

@article{d3a09b7411c14cb09138f55ad9cdf0f4,

title = "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 suppressionof erythropoiesis. Interleukin 12 (IL12) significantly boosts erythropoietic responses in murine models of malarialanaemia and decreased IL12 levels are associated with severe malarial anaemia (SMA) in children. Based on thebiological relevance of IL12 in malaria anaemia, the relationship between genetic polymorphisms of IL12 and itsreceptors and SMA was examined.Methods: Fifty-five tagging single nucleotide polymorphisms covering genes encoding two IL12 subunits, IL12Aand IL12B, and its receptors, IL12RB1 and IL12RB2, were examined in a cohort of 913 children residing in AsemboBay region of western Kenya.Results: An increasing copy number of minor variant (C) in IL12A (rs2243140) was significantly associated with adecreased 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 protectiveagainst 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 severeanaemia with any parasitaemia (SAP) (P = 0.004; risk ratio, 0.66). In contrast, AG genotype for another variant inIL12RB1 (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 IL12RB1and protection from SMA in Kenyan children, suggesting that human genetic variants of IL12 related genes maysignificantly contribute to the development of anaemia in malaria patients.",

author = "Lyna Zhang and Donald Prather and Eng, \{Jodi Vanden\} and Sara Crawford and Simon Kariuki and \{Ter Kuile\}, Feiko and Anja Terlouw and Bernard Nahlen and Lal, \{Altaf A.\} and Laurence Slutsker and Venkatachalam Udhayakumar and Shi, \{Ya Ping\}",

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doi = "10.1186/1475-2875-9-87",

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Zhang, L, Prather, D, Eng, JV, Crawford, S, Kariuki, S, Ter Kuile, F , Terlouw, A, Nahlen, B, Lal, AA, Slutsker, L, Udhayakumar, V & Shi, YP 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, no. 1, 87. https://doi.org/10.1186/1475-2875-9-87

TY - JOUR

T1 - Polymorphisms in genes of interleukin 12 and its receptors and their association with protection against severe malarial anaemia in children in western Kenya

AU - Zhang, Lyna

AU - Prather, Donald

AU - Eng, Jodi Vanden

AU - Crawford, Sara

AU - Kariuki, Simon

AU - Ter Kuile, Feiko

AU - Terlouw, Anja

AU - Nahlen, Bernard

AU - Lal, Altaf A.

AU - Slutsker, Laurence

AU - Udhayakumar, Venkatachalam

AU - Shi, Ya Ping

PY - 2010/3/29

Y1 - 2010/3/29

N2 - Background: Malarial anaemia is characterized by destruction of malaria infected red blood cells and suppressionof erythropoiesis. Interleukin 12 (IL12) significantly boosts erythropoietic responses in murine models of malarialanaemia and decreased IL12 levels are associated with severe malarial anaemia (SMA) in children. Based on thebiological relevance of IL12 in malaria anaemia, the relationship between genetic polymorphisms of IL12 and itsreceptors and SMA was examined.Methods: Fifty-five tagging single nucleotide polymorphisms covering genes encoding two IL12 subunits, IL12Aand IL12B, and its receptors, IL12RB1 and IL12RB2, were examined in a cohort of 913 children residing in AsemboBay region of western Kenya.Results: An increasing copy number of minor variant (C) in IL12A (rs2243140) was significantly associated with adecreased 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 protectiveagainst 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 severeanaemia with any parasitaemia (SAP) (P = 0.004; risk ratio, 0.66). In contrast, AG genotype for another variant inIL12RB1 (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 IL12RB1and protection from SMA in Kenyan children, suggesting that human genetic variants of IL12 related genes maysignificantly contribute to the development of anaemia in malaria patients.

AB - Background: Malarial anaemia is characterized by destruction of malaria infected red blood cells and suppressionof erythropoiesis. Interleukin 12 (IL12) significantly boosts erythropoietic responses in murine models of malarialanaemia and decreased IL12 levels are associated with severe malarial anaemia (SMA) in children. Based on thebiological relevance of IL12 in malaria anaemia, the relationship between genetic polymorphisms of IL12 and itsreceptors and SMA was examined.Methods: Fifty-five tagging single nucleotide polymorphisms covering genes encoding two IL12 subunits, IL12Aand IL12B, and its receptors, IL12RB1 and IL12RB2, were examined in a cohort of 913 children residing in AsemboBay region of western Kenya.Results: An increasing copy number of minor variant (C) in IL12A (rs2243140) was significantly associated with adecreased 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 protectiveagainst 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 severeanaemia with any parasitaemia (SAP) (P = 0.004; risk ratio, 0.66). In contrast, AG genotype for another variant inIL12RB1 (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 IL12RB1and protection from SMA in Kenyan children, suggesting that human genetic variants of IL12 related genes maysignificantly contribute to the development of anaemia in malaria patients.

U2 - 10.1186/1475-2875-9-87

DO - 10.1186/1475-2875-9-87

M3 - Article

SN - 1475-2875

VL - 9

JO - Malaria Journal

JF - Malaria Journal

IS - 1

M1 - 87

ER -

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

Abstract

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