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dc.contributor.authorChintana Phawongen_US
dc.contributor.authorCollins Oumaen_US
dc.contributor.authorPiyatida Tangteerawatanaen_US
dc.contributor.authorJarinee Thongshooben_US
dc.contributor.authorTom Wereen_US
dc.contributor.authorYuvadee Mahakunkijcharoenen_US
dc.contributor.authorDuangrurdee Wattanasirichaigoonen_US
dc.contributor.authorDouglas Jay Perkinsen_US
dc.contributor.authorSrisin Khusmithen_US
dc.contributor.otherMahidol Universityen_US
dc.contributor.otherUniversity of New Mexicoen_US
dc.contributor.otherMaseno Universityen_US
dc.contributor.otherSrinakharinwirot Universityen_US
dc.contributor.otherUniversity of New Mexico School of Medicineen_US
dc.identifier.citationImmunogenetics. Vol.62, No.6 (2010), 345-356en_US
dc.description.abstractPolymorphic 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.en_US
dc.rightsMahidol Universityen_US
dc.subjectBiochemistry, Genetics and Molecular Biologyen_US
dc.subjectImmunology and Microbiologyen_US
dc.titleHaplotypes of IL12B promoter polymorphisms condition susceptibility to severe malaria and functional changes in cytokine levels in Thai adultsen_US
Appears in Collections:Scopus 2006-2010

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