title: Polymorphisms of transporter associated with antigen processing type 1 (TAP1), proteasome subunit beta type 9 (PSMB9) and their common promoter in African children with different manifestations of malaria.
abstract: The distribution of gene variants of the antigen processing proteins transporter associated with antigen processing type 1 (TAP1) and proteasome subunit beta type 9 (PSMB9) and of their shared bidirectional promoter was assessed in children with either mild or severe malaria. The genetic study was performed on samples collected during a longitudinal study on malariometric indices in an area hyperendemic for Plasmodium falciparum malaria in Gabon. The allele frequencies of the genes did not differ between the mild and the severe malaria groups. The distributions of alleles among children with distinct phenotypes of severe malaria were similar. A negative association of hypoglycaemia with the PSMB9 promoter variant PSMB9-R was found (odds ratio 0.01; chi2=12.1; P<0.0005; Pc<0.03). The promoter allele TAP1-446G was associated with hyperparasitaemia and absence of hypoglycaemia. TAP1, PSMB9, and TAP1/PSMB9 promoter alleles were in strong linkage disequilibrium. DNA sequencing of the TAP1/PSMB9 promoter region revealed a previously unrecognized single nucleotide polymorphism 455 bp upstream of the TAP1 transcription start site.
authors.affiliation: Institute for Tropical Medicine and University Medicine in Berlin, Humboldt University Berlin, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Niesporek
authors.forename: C G
authors.initials: CG
authors.lastname: Meyer
authors.forename: P G
authors.initials: PG
authors.lastname: Kremsner
authors.forename: J
authors.initials: J
authors.lastname: May
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000349:Africa; D002648:Child; D003546:Cysteine Endopeptidases / Q000235:genetics*; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008137:Longitudinal Studies; D008288:Malaria / Q000235:genetics*; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012720:Severity of Illness Index
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; C073119:TAP1 protein, human; C071313:LMP-2 protein; D003546:Cysteine Endopeptidases