Molecular Genomics Unit, Clinical Pathology Department, Medical Ain Shams Research Institute (MASRI), School of Medicine, Ain Shams University, Cairo 11566, Egypt.
Medicinal Biochemistry and Molecular Biology Department, School of Medicine, Ain Shams University, Cairo 11566, Egypt.
Genes (Basel). 2021 May 28;12(6):830. doi: 10.3390/genes12060830.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection provides a critical host-immunological challenge.
We explore the effect of host-genetic variation in interferon-lambda-3 rs12979860, Tolloid Like-1 () rs17047200 and Discoidin domain receptor 1() rs4618569 on host response to respiratory viral infections and disease severity that may probe the mechanistic approach of allelic variation in virus-induced inflammatory responses.
141 COVID-19 positive patients and 100 healthy controls were tested for interferon-lambda-3 rs12979860, rs17047200 and DDR1 rs4618569 polymorphism by TaqMan probe-based genotyping. Different genotypes were assessed regarding the COVID-19 severity and prognosis.
There were statistically significant differences between the studied cases and control group with regard to the presence of comorbidities, total leucocytic count, lymphocytic count, CRP, serum LDH, ferritin and D-dimer ( < 0.01). The CC genotype of rs12979860 cytokine, the AA genotype of rs17047200 and the AA genotype of the rs4618569 variant of showed a higher incidence of COVID-19 compared to the others. There were significant differences between the rs4618569 variant of and the outcome of the disease, with the highest mortality in AG genotype 29 (60.4%) in comparison to 16 (33.3%) and 3 (6.2%) in the AA and GG genotypes, respectively ( = 0.007*), suggesting that the A allele is associated with a poor outcome in the disease.
Among people who carry C and A alleles of SNPs rs12979860 and rs17047200, respectively, the AG genotype of the DDR1 rs4618569 variant is correlated with a COVID-19 poor outcome. In those patients, the use of anti-, and therapy may be promising for personalized translational clinical practice.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染对宿主的免疫反应提出了严峻挑战。
本研究旨在探讨干扰素-λ-3(rs12979860)、Tolloid 样 1(rs17047200)和盘状结构域受体 1(rs4618569)的宿主遗传变异对呼吸道病毒感染和疾病严重程度的影响，从而探究等位基因变异在病毒诱导的炎症反应中的作用机制。
对 141 例 COVID-19 阳性患者和 100 例健康对照者进行干扰素-λ-3(rs12979860)、rs17047200 和 DDR1(rs4618569)多态性的 TaqMan 探针基因分型检测。评估不同基因型与 COVID-19 严重程度和预后的关系。
与对照组相比，研究病例组的合并症、白细胞总数、淋巴细胞计数、C 反应蛋白、血清乳酸脱氢酶、铁蛋白和 D-二聚体存在统计学差异（<0.01）。与其他基因型相比，rs12979860 细胞因子的 CC 基因型、rs17047200 的 AA 基因型和 rs4618569 变体的 AA 基因型与 COVID-19 的发生率更高。rs4618569 变体与疾病结局存在显著差异，AG 基因型的死亡率最高（29%，60.4%），与 AA 基因型（33.3%）和 GG 基因型（6.2%）相比，差异有统计学意义（=0.007*），提示 A 等位基因与疾病预后不良相关。
在携带 SNPrs12979860 和 rs17047200 的 C 和 A 等位基因的人群中，DDR1 rs4618569 变体的 AG 基因型与 COVID-19 的不良结局相关。在这些患者中，使用抗、和疗法可能对个性化转化临床实践具有重要意义。
