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印度东北部阿萨姆邦甲型 H1N1pdm09 病毒感染人群中 HLA Ⅰ类和Ⅱ类等位基因的多态性。

Polymorphism of HLA class I and class II alleles in influenza A(H1N1)pdm09 virus infected population of Assam, Northeast India.

机构信息

Virology Division, ICMR-Regional Medical Research Centre, N.E. Region, Dibrugarh, Assam, India.

Department of Bioengineering and Technology, Institute of Science and Technology, Gauhati University, Guwahati, Assam, India.

出版信息

J Med Virol. 2018 May;90(5):854-860. doi: 10.1002/jmv.25018. Epub 2018 Feb 5.

Abstract

Human leucocyte antigen (HLA) represents one of the most highly polymorphic systems which plays a central role in the immune response. Genetic polymorphism of HLA in influenza A(H1N1)pdm09 infected population may be an important factor in disease progression and severity that needs further probing. In this study, a total of 110 Influenza like illness patients were recruited from the population of Assam, Northeast India, from which 35 cases infected by A(H1N1)pdm09 viruses and 35 controls were typed for HLA-A, B and DRB1 locus by PCR-SSP method. A total of seven alleles of HLA-A, 16 alleles of HLA-B, and 11 alleles of HLA-DRB1 locus were identified. The most common alleles within each locus in cases were HLA-A11 (85.71%, P = 0.046), HLA-B35 (25%, P = 0.0001), and HLA-DRB115 (49.35%,  P = 0.133) as compared to the controls, HLA-A11 (40.82%), HLA-B35 (0.00%), and HLA-DRB115 (67.53%). The frequency of HLA-A11 and HLA-B35 were significantly higher in cases as compared to the controls. In DRB1 locus, HLA-DRB110 was significantly higher in cases (20.78%, P = 0.005) than that of controls (0.00%). Whereas, HLA-DRB115 showed a higher frequency in controls than in cases. In addition, HLA-DRB301 (P = 0.053), DRB401 (P = 1.000), and DRB501(P = 0.591) were also identified along with HLA-DRB1 haplotype. From this preliminary study, it is suspected that there may be a role of HLA-A11, HLA-B35 and HLA-DRB110 in conferring susceptibility to influenza A(H1N1)pdm09 infection in the study population. A larger extended study on HLA polymorphism may explain the association between HLA and influenza A(H1N1)pdm09 infection and provide insights for HLA restricted peptide based vaccines.

摘要

人类白细胞抗原 (HLA) 是最具多态性的系统之一,在免疫反应中起着核心作用。甲型流感病毒(H1N1)pdm09 感染人群中 HLA 的遗传多态性可能是疾病进展和严重程度的重要因素,需要进一步研究。本研究共招募了来自印度东北部阿萨姆邦的 110 例流感样疾病患者,其中 35 例感染了 A(H1N1)pdm09 病毒,35 例对照采用 PCR-SSP 方法对 HLA-A、B 和 DRB1 基因座进行分型。共鉴定出 7 种 HLA-A 等位基因、16 种 HLA-B 等位基因和 11 种 HLA-DRB1 等位基因。病例中每个基因座最常见的等位基因为 HLA-A11(85.71%,P=0.046)、HLA-B35(25%,P=0.0001)和 HLA-DRB115(49.35%,P=0.133),而对照组分别为 HLA-A11(40.82%)、HLA-B35(0.00%)和 HLA-DRB115(67.53%)。与对照组相比,病例中 HLA-A11 和 HLA-B35 的频率明显更高。在 DRB1 基因座中,病例中 HLA-DRB110 的频率明显高于对照组(20.78%,P=0.005)。而 HLA-DRB115 在对照组中的频率高于病例。此外,还鉴定出 HLA-DRB301(P=0.053)、DRB401(P=1.000)和 DRB501(P=0.591)与 HLA-DRB1 单倍型一起。从这项初步研究中,可以怀疑 HLA-A11、HLA-B35 和 HLA-DRB110 可能在赋予研究人群对甲型流感病毒(H1N1)pdm09 感染的易感性方面发挥作用。对 HLA 多态性的更大扩展研究可以解释 HLA 与甲型流感病毒(H1N1)pdm09 感染之间的关联,并为基于 HLA 限制性肽的疫苗提供见解。

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