Laboratório de Vírus Respiratórios e do Sarampo, National Influenza Center (NIC)/World Health Organization (WHO), Instituto Oswaldo Cruz/Fiocruz, Rio de Janeiro, Brazil.
Laboratório de Vírus Respiratórios e do Sarampo, National Influenza Center (NIC)/World Health Organization (WHO), Instituto Oswaldo Cruz/Fiocruz, Rio de Janeiro, Brazil.
Infect Genet Evol. 2019 Jan;67:55-59. doi: 10.1016/j.meegid.2018.10.024. Epub 2018 Oct 31.
Influenza is an acute and highly contagious viral respiratory infection that causes significant morbidity and mortality. The identification of host genetic factors associated with susceptibility and severity of influenza virus infection is of paramount importance. Previous studies evaluating the potential involvement of the CCR5Δ32 polymorphism (rs333), a 32 base pair deletion in CC motif chemokine receptor 5 (CCR5) gene, in severity and mortality of influenza A(H1N1)pdm09 infected individuals have been reported, but their results are quite conflicting.
The aim of this study was the evaluation of the CCR5Δ32 frequency in individuals with mild, severe and fatal influenza A(H1N1)pdm09 infection and its putative association with clinical and epidemiologic data.
PATIENTS/METHODS: A total of 432 individuals were included in this study and classified according to their clinical status, into the following groups: influenza like illness (ILI) (n = 153); severe acute respiratory infection (SARI) (n = 173) and fatal (n = 106) cases. The samples were collected in the post pandemic period, from 2012 to 2018. Individuals were further stratified according to their clinical and epidemiological data. The CCR5Δ32 variant was genotyped by PCR amplification and a subset of samples was further submitted to Sanger sequencing.
The different clinical groups (ILI, SARI and fatal) presented similar distribution of wt/wt and wt/Δ32 genotypes and CCR5Δ32 allele frequencies. Genotype Δ32/Δ32 was not detected in our study. Additionally, no association between wt/wt and wt/Δ32 genotypes and dyspnea, a clinical factor for influenza complications was found. Similarly, no significant differences in the distribution of wt/wt and wt/Δ32 genotypes and CCR5Δ32 variant allele frequencies were observed in samples from the different Brazilian geographical regions.
The CCR5Δ32 variant does not influence the susceptibility to influenza A(H1N1)pdm09 severe disease or mortality in individuals from Brazil.
流感是一种急性且高度传染性的病毒性呼吸道感染,可导致严重的发病率和死亡率。确定与流感病毒感染易感性和严重程度相关的宿主遗传因素至关重要。先前的研究评估了 CCR5Δ32 多态性(rs333),即 CC 基序趋化因子受体 5(CCR5)基因中的 32 个碱基对缺失,在甲型 H1N1pdm09 感染个体的严重程度和死亡率中的潜在作用,但结果存在较大争议。
本研究旨在评估轻度、重度和致命性甲型 H1N1pdm09 流感感染个体中 CCR5Δ32 频率及其与临床和流行病学数据的可能关联。
患者/方法:本研究共纳入 432 例个体,根据其临床状况分为以下组别:流感样疾病(ILI)(n=153);严重急性呼吸道感染(SARI)(n=173)和死亡(n=106)病例。这些样本是在大流行后期(2012 年至 2018 年)收集的。个体根据其临床和流行病学数据进一步分层。通过 PCR 扩增对 CCR5Δ32 变体进行基因分型,并对部分样本进行 Sanger 测序。
不同的临床组(ILI、SARI 和死亡)的 wt/wt 和 wt/Δ32 基因型以及 CCR5Δ32 等位基因频率分布相似。在本研究中未检测到基因型Δ32/Δ32。此外,wt/wt 和 wt/Δ32 基因型与呼吸困难(流感并发症的临床因素)之间无相关性。同样,在来自巴西不同地理区域的样本中,wt/wt 和 wt/Δ32 基因型以及 CCR5Δ32 变异等位基因频率的分布无显著差异。
在巴西个体中,CCR5Δ32 变体不会影响对甲型 H1N1pdm09 严重疾病或死亡率的易感性。