Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Department of Immunology, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
Appl Biochem Biotechnol. 2022 Aug;194(8):3507-3526. doi: 10.1007/s12010-022-03885-w. Epub 2022 Apr 7.
Coronavirus disease 2019 (COVID-19) is a severe disease caused by a new variant of beta-coronavirus that first appeared in China. Human genetic factors, including polymorphisms, serve pivotal roles in the high transmission of SARS-CoV-2 and the stubbornly progressing sickness seen in a small but significant percentage of infected people; however, but these factors remain ill-defined. A total of 288 COVID-19 patients and 288 controls were genotyped for TMPRSS2 polymorphisms using both restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) and amplification refractory mutation system (ARMS)-PCR techniques. Different genotypes of TMPRSS2 polymorphisms were compared in terms of disease susceptibility and mortality. The statistical analysis showed that minor alleles of all studied variants statistically increased the risk of COVID-19, except for the rs75603675 C > A variant. The T allele of rs12329760 conferred an increased risk of COVID-19. Moreover, the AG/AC/TT/AG combination of genotypes significantly enhanced the risk of COVID-19 in our population. Different haplotypes of rs17854725/rs75603675/rs12329760/rs4303795 polymorphisms, including GACA, GACG, GATG, GATA, AATA, ACCG, ACTG, ACTA, GCCA, and GCTG, were found to be associated with increased risk of the disease (odds ratio > 1). Regarding the clinical and paraclinical characteristics, a statistically significant difference was found between non-severe and severe forms except for gender, platelet, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and underlying diseases. In addition, case genotypes of TMPRSS2 rs17854725 A > G, rs12329760 C > T, and rs4303795 A > G were significantly different regarding severe and non-severe forms of the disease (P-value < 0.001). Specifically, death was more frequent in carriers of the AG genotype of rs17854725 A > G (P-value = 0.022). Patients who carry the minor alleles of the four studied TMPRSS2 variants were rather vulnerable to COVID-19 infection. Our findings indicated that rs17854725 A > G (AA vs. AG and AA vs. GG), rs12329760 C > T (CC vs. CT and CC vs. TT), and rs4303795 A > G (AA vs. AG) genotypes of TMPRSS2 variations are associated with a more invasive disorder pattern. More studies on larger populations are needed to confirm our results.
2019 年冠状病毒病（COVID-19）是由最初在中国出现的新型β冠状病毒引起的严重疾病。人类遗传因素，包括多态性，在 SARS-CoV-2 的高传播率和一小部分感染人群中疾病顽固进展中起着关键作用；然而，这些因素仍然定义不明确。使用限制性片段长度多态性聚合酶链反应（RFLP-PCR）和扩增受阻突变系统（ARMS）-PCR 技术对 288 例 COVID-19 患者和 288 例对照者的 TMPRSS2 多态性进行了基因分型。比较了不同 TMPRSS2 多态性基因型的疾病易感性和死亡率。统计分析表明，除 rs75603675 C > A 变体外，所有研究变体的次要等位基因均统计学上增加了 COVID-19 的风险。rs12329760 的 T 等位基因增加了 COVID-19 的风险。此外，我们人群中基因型 AG/AC/TT/AG 组合显著增加了 COVID-19 的风险。rs17854725/rs75603675/rs12329760/rs4303795 多态性的不同单倍型，包括 GACA、GACG、GATG、GATA、AATA、ACCG、ACTG、ACTA、GCCA 和 GCTG，与疾病风险增加（优势比> 1）相关。关于临床和临床前特征，除性别、血小板、C 反应蛋白（CRP）、红细胞沉降率（ESR）和潜在疾病外，非严重和严重形式之间存在统计学差异。此外，TMPRSS2 rs17854725 A > G、rs12329760 C > T 和 rs4303795 A > G 的病例基因型在严重和非严重疾病形式方面差异显著（P 值<0.001）。具体而言，携带 rs17854725 A > G（AG 基因型）的患者死亡更为频繁（P 值= 0.022）。携带四种研究的 TMPRSS2 变体的次要等位基因的患者更容易感染 COVID-19。我们的研究结果表明，rs17854725 A > G（AA 与 AG 和 AA 与 GG）、rs12329760 C > T（CC 与 CT 和 CC 与 TT）和 rs4303795 A > G（AA 与 AG）基因型与更具侵袭性的疾病模式相关。需要对更大的人群进行更多的研究来证实我们的结果。
