Association of ACE۲ and TMPRSS۲ genes polymorphisms in altering host susceptibility to SARS-COV-۲ virus

The Covid ۱۹ pandemic caused by SARS_COV_۲ (Acute Respiratory Coronavirus ۲ Syndrome) was first reported by the WHO in March ۲۰۲۰. The spike protein (S protein), a protein encoded by the virus, binds to ACE۲ (the enzyme angiotensin ۲), which acts as a receptor for the virus to enter the host. Then, the S protein causes the virus to enter the host cell through membrane processes, encoded by TMPRSS۲. ACE۲ and TMPRSS۲ genes are expressed in many human tissues, but the individual expression of these genes varies in different societies. Examination of ACE۲ and TMPRSS۲ gene polymorphisms in different populations has shown that these polymorphisms can increase the host susceptibility to SARS_COV_۲ or cause the host to become resistant to coronavirus infection. Extensive epidemiological studies have also been performed to investigate susceptibility to infection, severity of pathogenicity, and lethality of the virus in terms of gender and age differences. The obtained results showed that certain types of unique but common polymorphisms in TMPRSS۲, such as rs۱۲۳۲۹۷۶۰ and p.val۱۶۰.met, can alter the susceptibility of individuals and their lung tissue to SARS_COV_۲ virus infection. On the other hand, ACE۲ polymorphisms are significantly associated with the severity of SARS_COV_۲ virus infection. Based on studies, ۱۳ polymorphisms (including rs۲۰۹۷۷۲۳, rs۱۴۲۰۱۷۹۳۴ and rs۴۶۴۶۱۴۰) have been observed in the coding and non-coding sites of the ACE۲ gene, all of which alter the expression of the ACE۲ gene. Also, the study of gender factor in studies of ACE۲ gene polymorphisms has shown the association of some polymorphisms with higher rates of infection and infectivity in one sex than the other sex. Further studies on these polymorphisms in different communities can be an effective guide in finding a cure, discovering effective drugs, and designing effective vaccines against SARS-COV-۲.

Keywords:

Covid-۱۹ , s-protein , Genetic polymorphisms , ACE۲ genetic polymorphisms , Angiotensin receptor