Susceptible and Protective HLA Class 1 Alleles against Dengue Fever and Dengue Hemorrhagic Fever Patients in a Malaysian Population
Susceptible and Protective HLA Class 1 Alleles against Dengue Fever and Dengue Hemorrhagic Fever Patients in a Malaysian Population
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DOI：
10.1371/journal.pone.0013029
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发表时间：
2010-09-28
期刊：
影响因子：
3.7
通讯作者：
Sekaran, Shamala Devi
中科院分区：
文献类型：
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作者：
Appanna, Ramapraba;Ponnampalavanar, Sasheela;Sekaran, Shamala Devi
人类白细胞抗原等位基因已被认为是预测登革病毒（DENV）感染的易感性和/或保护性的可能遗传标记。在本研究中，我们的目的是调查的第一次，HLA 1类（-A和-B）的DENV感染的患者对健康individualinMalaysia.Methodology/Principal Findings的基因型变异：本研究进行了92登革热病患者和95名健康对照从三个不同的种族（马来人，中国人和印度人）在马来西亚。使用聚合酶链反应-序列特异性引物技术，对所有临床和实验室确诊为DENV感染的患者进行HLA-A和B位点分型。在我们的总人群中，与健康供体相比，DHF患者的HLA-B *53（P=0.042，Pc=1.008）等位基因显著增加，A*03（P=0.015，Pc=0.18，OR=5.23，95%CI =1.19-23.02）和B*18（P=0.017，Pc=0.408）等位基因显著减少。我们还观察到，在马来DHF患者中，等位基因B*13（P=0.049，Pc=1.176，OR=0.18，95%CI =0.03-0.90），而HLA-B*18等位基因在该人群中的频率显著高于其他等位基因（P = 0.049，Pc = 1.176，OR = 0.18，95%CI =0.03-0.90），而HLA-B*18等位基因在该人群中的频率显著高于其他等位基因（P = 0.001）。（P=0.024，Pc=0.576）被认为是负相关的DHF.结论/意义：这些是在我们的人口中的遗传多态性的第一个发现，我们得出结论：（1）在我们的总人群中，HLA-B*53可能与疾病易感性有关，而HLA-A*03和HLA-B*18可能提供保护，使其免于进展为严重疾病;（2）在马来人人群中，HLA-B*13和B*18可能分别与疾病易感性和保护有关。这些结果可以作为一个有价值的预测工具，以确定不同种族的个体在风险和/或保护严重形式的登革病毒感染，并将提供有价值的信息，为未来的登革疫苗的设计。
The human leukocyte antigen alleles have been implicated as probable genetic markers in predicting the susceptibility and/or protection to severe manifestations of dengue virus (DENV) infection. In this present study, we aimed to investigate for the first time, the genotype variants of HLA Class 1(-A and -B) of DENV infected patients against healthy individuals in Malaysia.Methodology/Principal Findings: This study was carried out with 92 dengue disease patients and 95 healthy controls from three different ethnic groups (Malay, Chinese and Indian) in Malaysia. All patients with clinical and laboratory confirmation of DENV infection were typed for the HLA-A and B loci, using polymerase chain reaction-sequence specific primer techniques. In our total population, a significant increase for HLA-B*53 (P=0.042, Pc=1.008) allele and a significant decrease for A*03 (P=0.015, Pc=0.18, OR=5.23, 95% CI=1.19-23.02) and B*18 (P=0.017, Pc=0.408) alleles were noted in DHF patients as compared to healthy donors. We also observed that in the Malay DHF patients, allele B*13 (P=0.049, Pc=1.176, OR=0.18, 95% CI=0.03-0.90) was present at a significantly higher frequency in this population while allele HLA-B*18 (P=0.024, Pc=0.576) was seen to be negatively associated with DHF.Conclusions/Significance: These are the first findings on genetic polymorphisms in our population and we conclude that: (1) In our total population, HLA-B*53 probably involve in disease susceptibility, while the HLA-A*03 and HLA-B*18 may confer protection from progression to severe disease; (2) In the Malay population, HLA-B*13 and B*18 are probably associated in disease susceptibility and protection, respectively. These results could furnish as a valuable predictive tool to identify ethnically different individuals at risk and/or protection from severe forms of DENV infection and would provide valuable informations for the design of future dengue vaccine.