A STAT6 Intronic Single-Nucleotide Polymorphism is Associated with Clinical Malaria in Ghanaian Children.
Malaria pathogenesis may be influenced by IgE responses and cytokine cross-regulation. Several mutations in the IL-4/STAT6 signaling pathway can alter cytokine cross-regulation and IgE responses during a Plasmodium falciparum malarial infection. This study investigated the relationship between a STAT6 intronic single-nucleotide polymorphism (rs3024974), total IgE, cytokines, and malaria severity in 238 Ghanaian children aged between 0.5 and 13 years. Total IgE and cytokine levels were measured by ELISA, while genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (RFLP). Compared with healthy controls, heterozygosity protected against clinical malaria: uncomplicated malaria (odds ratios [OR] = 0.13, P < 0.001), severe malarial anemia (OR = 0.18, P < 0.001), and cerebral malaria (OR = 0.39, P = 0.022). Levels of total IgE significantly differed among malaria phenotypes (P = 0.044) and rs3024974 genotypes (P = 0.037). Neither cytokine levels nor IL-6/IL-10 ratios were associated with malaria phenotypes or rs3024974 genotypes. This study suggests a role for rs3024974 in malaria pathogenesis and offers further insights into an IL-4/STAT6 pathway mutation in malaria pathogenesis.
Department of Microbiology and Immunology, School of Medical Sciences, College of Health and Allied Sciences, University of Cape Coast, Cape Coast, Ghana.; Immunology Department, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Accra, Ghana.
Daniel
D
Amoako-Sakyi
Immunology Department, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Accra, Ghana.; Institute of Tropical Medicine, Eberhard Karls University, Tübingen, Germany.
Selorme
S
Adukpo
Immunology Department, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Accra, Ghana.
Kwadwo A
KA
Kusi
Immunology Department, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Accra, Ghana.
Daniel
D
Dodoo
Immunology Department, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Accra, Ghana.
Michael F
MF
Ofori
Department of Child Health, School of Medicine and Dentistry, College of Health Science, University of Ghana, Legon, Accra, Ghana.; Centre for Tropical Clinical Pharmacology and Therapeutics, School of Medicine and Dentistry, Centre for Tropical Clinical Pharmacology and Therapeutics, Legon, Accra, Ghana.
George O
GO
Adjei
Department of Animal Biology and Conservation Science, University of Ghana, Legon, Accra, Ghana.
Dominic E
DE
Edoh
Department of Medical Laboratory Sciences, School of Allied Health Sciences, College of Health Sciences, University of Ghana, Legon, Accra, Ghana.
Richard H
RH
Asmah
Department of Medical Laboratory Sciences, School of Allied Health Sciences, College of Health Sciences, University of Ghana, Legon, Accra, Ghana.
Charles
C
Brown
Immunology Department, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Accra, Ghana.
Bright
B
Adu
Department of Microbiology and Immunology, School of Medical Sciences, College of Health and Allied Sciences, University of Cape Coast, Cape Coast, Ghana.
Dorcas
D
Obiri-Yeboah
Department of Animal Biology and Conservation Science, University of Ghana, Legon, Accra, Ghana.
Godfred
G
Futagbi
Department of Microbiology and Immunology, School of Medical Sciences, College of Health and Allied Sciences, University of Cape Coast, Cape Coast, Ghana.
Sharif Buari
SB
Abubakari
Department of Molecular Biosciences, Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
Marita
M
Troye-Blomberg
Immunization and Vaccines Development Programme, Family & Reproductive Health Cluster, WHO Regional Office for Africa, Brazzaville, Congo.
Bartholomew D
BD
Akanmori
Department of Child Health, School of Medicine and Dentistry, College of Health Science, University of Ghana, Legon, Accra, Ghana.
Bamenla Q
BQ
Goka
Department of Biological, Environmental and Occupational Health, School of Public Health, College of Health Sciences, University of Ghana, Legon, Accra, Ghana.
John
J
Arko-Mensah
Immunology Department, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Accra, Ghana.
Ben A
BA
Gyan
Ghana; IgE; SNP; STAT6; intron; malaria; rs3024974