Abu-Almfalfal Razan Issam, Jarrar Yazun Bashir, Gharaibeh Munir
Department of Pharmacology, Faculty of Medicine, The University of Jordan, Amman, Jordan.
Department of Basic Medical Sciences, Faculty of Medicine, Al-Balqa Applied University, Al-Salt, Jordan.
Ann Hum Genet. 2025 May;89(2-3):96-105. doi: 10.1111/ahg.12588. Epub 2024 Dec 27.
The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become a global health concern. The entry of the virus into host cells is facilitated by the transmembrane protease serine 2 (TMPRSS2) receptor, and genetic variations in the TMPRSS2 gene may influence disease susceptibility. However, there is a lack of knowledge regarding TMPRSS2 genetic variants and haplotypes in the Jordanian population.
This study aimed to characterize the genotype and haplotype variations in the TMPRSS2 binding domain with SARS-CoV-2 among Jordanian volunteers.
The binding domain of TMPRSS2 with SARS-CoV-2 (Exons 9 and 10) was amplified using polymerase chain reaction (PCR) for a random sample of 120 healthy unrelated Jordanian volunteers, followed by Sanger DNA sequencing for the PCR products. The effect of the novel genetic variants on the TMPRSS2 protein structure was predicted using in silico methods.
The results showed significant (p < 0.05, chi-square) allele frequencies for known TMPRSS2 variants, with c.888C > T being the most prevalent among Jordanian volunteers. Novel genetic variants, including c.869A > G and c.923T > A, were also identified, with the latter being the most common novel variant. Haplotype analysis showed that the most prevalent TMPRSS2 haplotype is c.911G/1051A/1052T/1010 + 45C/1011 - 38T/1011 - 52C/1011 - 54A. In silico programs predicted that TMPRSS2 c.923T > A and c.1052T > A variants affect transmembrane proteins and catalytic sites.
This research provides information about the gene structure of the TMPRSS2 binding domain in Jordanians. Some of the identified variants, especially c.923T > A, may influence protein function, warranting further in vitro and in vivo investigations. In addition, further clinical research studies are needed to link the identified TMPRSS2 variants with COVID-19 susceptibility and severity among Jordanians.
由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起的2019冠状病毒病（COVID-19）已迅速成为全球卫生关注的焦点。跨膜蛋白酶丝氨酸2（TMPRSS2）受体有助于病毒进入宿主细胞，TMPRSS2基因的遗传变异可能影响疾病易感性。然而，关于约旦人群中TMPRSS2基因变异和单倍型的了解尚少。
本研究旨在对约旦志愿者中TMPRSS2与SARS-CoV-2结合域的基因型和单倍型变异进行特征分析。
对120名健康、无亲缘关系的约旦志愿者随机样本，采用聚合酶链反应（PCR）扩增TMPRSS2与SARS-CoV-2的结合域（外显子9和10），随后对PCR产物进行桑格DNA测序。使用计算机模拟方法预测新的基因变异对TMPRSS2蛋白结构的影响。
结果显示，已知TMPRSS2变异的等位基因频率具有显著性（p < 0.05，卡方检验），其中c.888C>T在约旦志愿者中最为常见。还鉴定出了新的基因变异，包括c.869A>G和c.923T>A，后者是最常见的新变异。单倍型分析表明，最常见的TMPRSS2单倍型是c.911G/1051A/1052T/1010 + 45C/1011 - 38T/1011 - 52C/1011 - 54A。计算机模拟程序预测，TMPRSS2的c.923T>A和c.1052T>A变异会影响跨膜蛋白和催化位点。
本研究提供了约旦人TMPRSS2结合域基因结构的信息。一些已鉴定出的变异，尤其是c.923T>A，可能影响蛋白质功能，需要进一步进行体外和体内研究。此外，还需要进一步的临床研究，以将已鉴定出的TMPRSS2变异与约旦人对COVID-19的易感性和严重程度联系起来。
