title: IFNGR1 gene promoter polymorphisms and susceptibility to cerebral malaria.
abstract: Interferon (IFN)-gamma is a critical mediator of immunity to malaria. This study explored the relationship between polymorphisms in the promoter region of the gene encoding IFN-gamma receptor 1 (IFNGR1) and susceptibility to malaria in African children. Four polymorphisms were found in the region between -1400 and +100 nt of the translational start site by sequencing, and analysis of 562 nuclear families revealed 6 haplotypes. Case-control analysis of 562 Gambian children with severe malaria and 569 umbilical cord blood samples (controls) showed that in Mandinka, the major Gambian ethnic group, heterozygotes for the IFNGR1-56 polymorphism were protected against cerebral malaria (odds ratio, 0.54; P=.016) and against death resulting from cerebral malaria (odds ratio, 0.22; P=.006). Analysis of a family study by transmission disequilibrium testing revealed a similar result. Further data are needed to validate this finding, but these results are reminiscent of those for other well-established heterozygote advantages, such as that associated with hemoglobin S.
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, United Kingdom. oliverk@well.ox.ac.uk
authors.forename: Oliver
authors.initials: O
authors.lastname: Koch
authors.forename: Agnes
authors.initials: A
authors.lastname: Awomoyi
authors.forename: Stanley
authors.initials: S
authors.lastname: Usen
authors.forename: Muminatou
authors.initials: M
authors.lastname: Jallow
authors.forename: Anna
authors.initials: A
authors.lastname: Richardson
authors.forename: Jeremy
authors.initials: J
authors.lastname: Hull
authors.forename: Margaret
authors.initials: M
authors.lastname: Pinder
authors.forename: Melanie
authors.initials: M
authors.lastname: Newport
authors.forename: Dominic
authors.initials: D
authors.lastname: Kwiatkowski
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005190:Family; D005260:Female; D005714:Gambia; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D016779:Malaria, Cerebral / Q000235:genetics*; D008297:Male; D009154:Mutation; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017471:Receptors, Interferon / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D000096743:Interferon gamma Receptor
chemical_list: D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor