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疟疾不同临床表现的非洲儿童中与抗原加工相关转运体1型(TAP1)、蛋白酶体亚基β9型(PSMB9)及其共同启动子的多态性

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.

作者信息

Niesporek S, Meyer C G, Kremsner P G, May J

机构信息

Institute for Tropical Medicine and University Medicine in Berlin, Humboldt University Berlin, Germany.

出版信息

Int J Immunogenet. 2005 Feb;32(1):7-11. doi: 10.1111/j.1744-313X.2005.00484.x.


DOI:10.1111/j.1744-313X.2005.00484.x
PMID:15686587
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.

摘要

在患有轻度或重度疟疾的儿童中,评估了与抗原加工相关的转运蛋白1型(TAP1)和蛋白酶体亚基β9型(PSMB9)这两种抗原加工蛋白的基因变体及其共享双向启动子的分布情况。这项基因研究是基于在加蓬恶性疟高度流行地区进行的一项疟疾指标纵向研究期间收集的样本开展的。轻度和重度疟疾组之间这些基因的等位基因频率没有差异。不同严重疟疾表型的儿童中等位基因的分布相似。发现低血糖与PSMB9启动子变体PSMB9-R呈负相关(比值比0.01;卡方=12.1;P<0.0005;校正P<0.03)。启动子等位基因TAP1-446G与高疟原虫血症和无低血糖相关。TAP1、PSMB9和TAP1/PSMB9启动子等位基因处于强连锁不平衡状态。TAP1/PSMB9启动子区域的DNA测序揭示了TAP1转录起始位点上游455 bp处一个以前未被识别的单核苷酸多态性。

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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.

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