Publication:
Haplotypes of IL12B promoter polymorphisms condition susceptibility to severe malaria and functional changes in cytokine levels in Thai adults

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Issued Date

2010

Resource Type

Article

File Type

application/pdf

ISSN

937711

DOI

10.1007/s00251-010-0439-y

Other identifier(s)

2-s2.0-77953153281

Rights Holder(s)

Scopus

Bibliographic Citation

Immunogenetics. Vol 62, No.6 (2010), p.345-356

Suggested Citation

Phawong C., Ouma C., Tangteerawatana P., Thongshoob J., Were T., Mahakunkijcharoen Y., Wattanasirichaigoon D., Perkins D.J., Khusmith S. Haplotypes of IL12B promoter polymorphisms condition susceptibility to severe malaria and functional changes in cytokine levels in Thai adults. Immunogenetics. Vol 62, No.6 (2010), p.345-356. doi:10.1007/s00251-010-0439-y Retrieved from: https://hdl.handle.net/20.500.14740/7690

Title

Haplotypes of IL12B promoter polymorphisms condition susceptibility to severe malaria and functional changes in cytokine levels in Thai adults

Author(s)

Phawong C.
 Ouma C.
 Tangteerawatana P.
 Thongshoob J.
 Were T.
 Mahakunkijcharoen Y.
 Wattanasirichaigoon D.
 Perkins D.J.
 Khusmith S.

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.

Subject(s)

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

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https://hdl.handle.net/20.500.14740/7690

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Scopus: Year 1983-2021

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