Free Content Associations between frequencies of a susceptible TNF-α promoter allele and protective α-thalassaemias and malaria parasite incidence in Vanuatu

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Tumour necrosis factor-alpha (TNF-α) is one of the key cytokines that influence the pathology of microbial infections. The genetic susceptibility to severe forms of falciparum malaria is differentially associated with TNF-α promoter gene polymorphisms (TNFP alleles). In a previous study, we identified a TNFP-allele characterized by a C to T transition at position −857 (TNFP-D allele) as a marker for susceptibility to cerebral malaria in Myanmar. The frequencies of TNFP alleles on six islands of Vanuatu, Melanesia (South-west Pacific) were estimated to investigate whether malaria selection pressure on this susceptibility marker has influenced its prevalence. Within the archipelago of Vanuatu there is a decreasing cline of parasite incidence from North to South. Of the four alleles of the TNFP gene detected in Vanuatu, the TNFP-D allele frequencies were inversely correlated with the parasite incidence of islands; TNFP-D varied from 0.55 on the island with the lowest parasite incidence to 0.26 on the island with the highest parasite incidence (r = −0.855, P = 0.03). We also observed a significant correlation between the frequencies of α-thalassaemia alleles, thought to protect against malaria and parasite incidence in the same populations. These data are consistent with a previously reported correspondence between the frequencies of glucose 6-phosphate dehydrogenase (G6PD) deficiency and parasite incidences on the islands of Vanuatu ( Kaneko et al. 1998 ) and indicate that the degree of malaria endemicity has influenced the allele frequencies of at least three loci that confer both susceptibility (TNFP-D) and protection (α-thalassaemias and G6PD deficiency).

Keywords: Melanesia; TNF-α; malaria; selection; α-thalassaemia

Document Type: Research Article


Affiliations: 1: Department of Molecular Immunogenetics, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan 2: Department of International Affairs and Tropical Medicine, Tokyo Women's Medical University, Tokyo, Japan 3: Department of Anthropology, Binghamton University, Binghamton, NY, USA

Publication date: June 1, 2005

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