Details:

Alternative Title:
Malar J
Personal Author:
Zhang, Lyna ; Prather, Donald ; Eng, Jodi Vanden ; Crawford, Sara ; Kariuki, Simon ; ... More +
Zhang, Lyna ; Prather, Donald ; Eng, Jodi Vanden ; Crawford, Sara ; Kariuki, Simon ; ter Kuile, Feiko ; Terlouw, Dianne ; Nahlen, Bernard ; Lal, Altaf A ; Slutsker, Laurence ; Udhayakumar, Venkatachalam ; Shi, Ya Ping Less -
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.


Subject:
[+]
Anemia
Child, Preschool
Cohort Studies
Female
Follow-Up Studies
Genetic Predisposition To Disease
Genotype
Humans
Infant
Infant, Newborn
Interleukin-12 Subunit P35
Malaria
Male
Phenotype
Plasmodium Falciparum
Polymorphism, Single Nucleotide
Receptors, Interleukin-12
Research

Source:
Malar J. 2010; 9:87.
Document Type:
Journal Article
Place as Subject:
Kenya
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:5b6f3df27ecdd3f8cd2ffe8af81e1c1a872c957ed6cacc4e14e18b351a6a00a1
File Type:

Supporting Files

• 	1475-2875-9-87-1.gif	gif
  	1475-2875-9-87-1.jpg	jpeg
  	1475-2875-9-87-S1.XLS	xls
  	1475-2875-9-87.nxml	txt
  	license.txt	txt

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