Please use this identifier to cite or link to this item: http://ir.swu.ac.th/jspui/handle/123456789/14782
Title: Haplotypes of IL12B promoter polymorphisms condition susceptibility to severe malaria and functional changes in cytokine levels in Thai adults
Authors: Phawong C.
Ouma C.
Tangteerawatana P.
Thongshoob J.
Were T.
Mahakunkijcharoen Y.
Wattanasirichaigoon D.
Perkins D.J.
Khusmith S.
Keywords: gamma interferon
interleukin 12p40
gamma interferon
interleukin 12
interleukin 12p40
adult
aged
article
cytokine production
disease association
disease severity
DNA extraction
DNA polymorphism
enzyme linked immunosorbent assay
gene amplification
genotype
haplotype
human
major clinical study
malaria
nonhuman
parasitemia
Plasmodium falciparum
priority journal
protein blood level
Thailand
3' untranslated region
adolescent
blood
female
genetic polymorphism
genetic predisposition
genetics
haplotype
immunology
malaria falciparum
male
middle aged
promoter region
Plasmodium falciparum
3' Untranslated Regions
Adolescent
Adult
Aged
Female
Genetic Predisposition to Disease
Genotype
Haplotypes
Humans
Interferon-gamma
Interleukin-12
Interleukin-12 Subunit p40
Malaria, Falciparum
Male
Middle Aged
Parasitemia
Polymorphism, Genetic
Promoter Regions, Genetic
Issue Date: 2010
Abstract: Polymorphic variability in immune response genes, such as IL12B, encoding the IL-12p40 subunit is associated with susceptibility to severe malaria in African populations. Since the role of genetic variation in conditioning severe malaria in Thai adults is largely unexplored, the functional association between IL12B polymorphisms [i.e. IL12Bpro (rs17860508) and IL12B 3′ UTR T/G (rs3212227)], severe malaria and cytokine production was examined in patients with Plasmodium falciparum infections (n=355) recruited from malaria endemic areas along the Thai-Myanmar border in northwest Thailand. Circulating IL-12p40 (p=0.049) and IFN-γ (p=0.051) were elevated in patients with severe malaria, while only IL-12p40 was significantly higher in severe malaria patients with hyperparasitaemia (p=0.046). Carriage of the IL12Bpro1.1 genotype was associated with enhanced severity of malaria (OR, 2.34; 95% CI, 0.94-5.81; p=0.066) and hyperparasitaemia (OR, 3.42; 95% CI, 1.17-9.87; p=0.025) relative to the IL12Bpro2.2 genotype (wild type). Individuals with the IL12Bpro1.1 genotype also had the lowest IL-12p40 (p=0.002) and the highest IFN-γ (p=0.004) levels. Construction of haplotypes revealed that carriage of the IL12Bpro-2/3′ UTR-T haplotype was associated with protection against severe malaria (OR, 0.51; 95% CI, 0.29-0.90; p=0.020) and reduced circulating IFN-γ (p=0.06). Thus, genotypic and haplotypic variation at IL12Bpro and IL12B 3′ UTR in this population influences susceptibility to severe malaria and functional changes in circulating IL-12p40 and IFN-γ levels. Results presented here suggest that protection against severe malaria in Thai adults is associated with genotypic variants that condition enhanced IL-12p40 and reduced IFN-γ levels. © 2010 Springer-Verlag.
URI: https://www.scopus.com/inward/record.uri?eid=2-s2.0-77953153281&doi=10.1007%2fs00251-010-0439-y&partnerID=40&md5=64e0ad14305343afdee4d38f34c43d4b
http://ir.swu.ac.th/jspui/handle/123456789/14782
ISSN: 937711
Appears in Collections:Scopus 1983-2021

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