Soundravally R, Hoti S L
Department of Molecular Biology and Bioinformatics, Vector Control Research Centre (VCRC), Pondicherry, South India.
J Clin Immunol. 2008 May;28(3):256-62. doi: 10.1007/s10875-007-9154-3.
The polymorphic transporter associated with antigen processing (TAP)1 and TAP2 genes encode subunits of the transporter that delivers peptides to the human leukocyte antigen class I molecules. Because the polymorphism of the TAP genes has been shown to affect peptide transport, it has been suggested that TAP genes are potential regulators of the immune response. We recently reported that TAP1 gene polymorphism is associated with severe dengue infection. This study was carried out to elucidate whether TAP2 polymorphisms are involved in diverse pathogenesis of dengue infection.
This study included 100 controls and 197 dengue-infected patients who were further categorized into 90 dengue fever (DF) cases, 75 dengue hemorrhagic fever cases (DHF), and 32 dengue shock syndrome (DSS) cases as per WHO grading system. TAP2 gene polymorphisms were determined by amplification refraction mutation system-polymerase chain reaction.
The frequency of isoleucine at TAP2 379 (34.5%) was increased among DHF in comparison to controls (21%, P = 0.014). DHF cases were more likely to be heterozygous at TAP2 379 (50.7%) than controls [24%, odds ratio (OR) = 2.11, P = 0.001]. Significantly high proportion of DHF was found to have TAP2 665 threonine/alanine (THR/ALA) genotypes (30.7%) when compared with DF (13.3%, OR = 2.3, P = 0.006) cases. There was no difference in the genotypes studied between DSS and controls or DF or DHF.
This first report on TAP 2 gene polymorphism in dengue suggested that heterozygous pattern at TAP2 379 locus confers susceptibility to DHF, and TAP2 665 THR/ALA genotype was found to be a risk factor for development of DHF.
与抗原加工相关的多态性转运体（TAP）1和TAP2基因编码将肽递送至人类白细胞抗原I类分子的转运体亚基。由于已表明TAP基因的多态性会影响肽转运，因此有人提出TAP基因是免疫反应的潜在调节因子。我们最近报告称，TAP1基因多态性与严重登革热感染有关。本研究旨在阐明TAP2多态性是否参与登革热感染的多种发病机制。
本研究纳入了100名对照者和197名登革热感染患者，根据世界卫生组织分级系统，这些患者进一步分为90例登革热（DF）病例、75例登革出血热（DHF）病例和32例登革休克综合征（DSS）病例。通过扩增折射突变系统-聚合酶链反应确定TAP2基因多态性。
与对照组（21%）相比，DHF患者中TAP2 379位点异亮氨酸的频率（34.5%）增加（P = 0.014）。DHF病例在TAP2 379位点杂合的可能性（50.7%）高于对照组[24%，优势比（OR）= 2.11，P = 0.001]。与DF（13.3%，OR = 2.3，P = 0.006）病例相比，发现DHF中TAP2 665苏氨酸/丙氨酸（THR/ALA）基因型的比例显著较高（30.7%）。DSS与对照组、DF或DHF之间在所研究的基因型上没有差异。
关于登革热中TAP 2基因多态性的这一首次报告表明，TAP2 379位点的杂合模式使个体易患DHF，并且发现TAP2 665 THR/ALA基因型是DHF发生的一个危险因素。
