IFNGR1 gene promoter polymorphisms and susceptibility to cerebral malaria

被引:81
作者
Koch, O
Awomoyi, A
Usen, S
Jallow, M
Richardson, A
Hull, J
Pinder, M
Newport, M
Kwiatkowski, D
机构
[1] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England
[2] Univ Oxford, Dept Pediat, Oxford OX3 7BN, England
[3] MRC Labs, Fajara, Gambia
[4] Royal Victoria Hosp, Banjul, Gambia
基金
英国医学研究理事会;
关键词
D O I
10.1086/340516
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:1684 / 1687
页数:4
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