严重急性呼吸道综合征冠状病毒2(SARS-CoV-2)感染提供了关键的宿主免疫挑战。
我们探讨了干扰素-λ-3rs12979860,TolloidLike-1(TLL1)rs17047200和盘状结构域受体1(DDR1)rs4618569中宿主遗传变异对宿主对呼吸道病毒感染的反应和疾病严重程度的影响,这可能是病毒诱导的炎症反应中等位基因变异的机制方法。
通过基于TaqMan探针的基因分型,对141例COVID-19阳性患者和100例健康对照进行了干扰素-λ-3rs12979860、TLL1rs17047200和DDR1rs4618569多态性检测。评估了不同基因型的COVID-19严重程度和预后。
在合并症的存在方面,研究病例与对照组之间存在统计学上的显着差异,总白细胞计数,淋巴细胞计数,CRP,血清LDH,铁蛋白和D-二聚体(p<0.01)。rs12979860细胞因子CC基因型,TLL1rs17047200的AA基因型和DDR1的rs4618569变体的AA基因型显示,与其他基因型相比,COVID-19的发病率更高。DDR的rs4618569变体与疾病的预后之间存在显着差异,与AA和GG基因型中的16(33.3%)和3(6.2%)相比,AG基因型29的死亡率最高(60.4%),分别(p=0.007*),表明A等位基因与疾病的不良结局有关。
在分别携带IFN-λrs12979860和TLL1rs17047200的SNP的C和A等位基因的人群中,DDR1rs4618569变异体的AG基因型与COVID-19不良结局相关。在这些患者中,使用抗IFN-λ3、TLL1和DDR1治疗可能有希望用于个性化转化临床实践。
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 (TLL1) rs17047200 and Discoidin domain receptor 1(DDR1) 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, TLL1 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 (p < 0.01). The CC genotype of rs12979860 cytokine, the AA genotype of TLL1 rs17047200 and the AA genotype of the rs4618569 variant of DDR1 showed a higher incidence of COVID-19 compared to the others. There were significant differences between the rs4618569 variant of DDR 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 (p = 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 IFN-λ rs12979860 and TLL1 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-IFN-λ 3, TLL1 and DDR1 therapy may be promising for personalized translational clinical practice.