title: Triosephosphate isomerase gene promoter variation: -5G/A and -8G/A polymorphisms in clinical malaria groups in two African populations.
abstract: TPI1 promoter polymorphisms occur in high prevalence in individuals from African origin. Malaria-patients from Angola and Mozambique were screened for the TPI1 gene promoter variants rs1800200A>G, (-5G>A), rs1800201G>A, (-8G>A), rs1800202T>G, (-24T>G), and for the intron 5 polymorphism rs2071069G>A, (2262G>A). -5G>A and -8G>A variants occur in 47% and 53% in Angola and Mozambique, respectively while -24T>G was monomorphic for the wild-type T allele. Six haplotypes were identified and -8A occurred in 45% of the individuals, especially associated with the GAG haplotype and more frequent in non-severe malaria groups, although not significantly. The arising and dispersion of -5G>A and -8G>A polymorphisms is controversial. Their age was estimated by analyses of two microsatellite loci, CD4 and ATN1, adjacent to TPI1 gene. The -5G>A is older than -8G>A, with an average estimate of approximately 35,000 years. The -8A variant arose in two different backgrounds, suggesting independent mutational events. The first, on the -5G background, may have occurred in East Africa around 20,800 years ago; the second, on the -5A background, may have occurred in West Africa some 7500 years ago. These estimates are within the period of spread of agriculture and the malaria mosquito vector in Africa, which could has been a possible reason for the selection of -8A polymorphism in malaria endemic countries.
authors: Centro de Malária e outras Doenças Tropicais, Unidade de Parasitologia Médica, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Portugal.
authors: Mónica
authors: M
authors: Guerra
authors: Centro de Malária e outras Doenças Tropicais, Unidade de Parasitologia Médica, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Portugal.
authors: Patrícia
authors: P
authors: Machado
authors: Centro de Investigação em Antropologia e Saúde (CIAS), Universidade de Coimbra, Portugal.
authors: Licínio
authors: L
authors: Manco
authors: Faculdade de Medicina da Universidade Eduardo Mondlane, Maputo, Mozambique.
authors: Natércia
authors: N
authors: Fernandes
authors: Hospital Pediátrico David Bernardino, Luanda, Angola.
authors: Juliana
authors: J
authors: Miranda
authors: Centro de Malária e outras Doenças Tropicais, Unidade de Parasitologia Médica, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Portugal. Electronic address: aparez@ihmt.unl.pt.
authors: Ana Paula
authors: AP
authors: Arez
mesh_terms: D000483:Alleles; D000810:Angola; D044383:Black People / Q000235:genetics*; D005787:Gene Frequency; D056426:Genetic Loci; D006239:Haplotypes; D006801:Humans; D007438:Introns; D008288:Malaria / Q000235:genetics*; D018895:Microsatellite Repeats; D009073:Mozambique; D010963:Plasmodium falciparum; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D014305:Triose-Phosphate Isomerase / Q000235:genetics*
chemical_list: D014305:Triose-Phosphate Isomerase
keywords: Human malaria; Selection signatures; TPI1 gene promoter variants; Triosephosphate isomerase-deficiency