Association of the polymorphism of the genes coding the renin-angiotensin system and the LZTFL1 gene with the severity and outcomes of SARS-CoV-2 infection

The aim of the study is to establish the association of variants of a number of genes involved in the reninangiotensin system with the severity of SARS-CoV-2 infection.

The study included 206 hospitalized patients with COVID-19: Group 1 – 99 patients with severe COVID-19; Group 2 ‒ 107 with moderate and mild forms of the disease.

Polymorphic variants of the ACE rs4646994, ACE2 rs2074192 rs2285666 and rs413031713 and LZTFL1 rs10490770 genes were analyzed using quantitative PCR with TaqMan probes (Primetech, Belarus) on a CFX96 thermocycler (Bio-Rad, USA). AGT rs699 and AGTR1 rs5186 gene variants were determined using a Rotor-Gene Q thermocycler (QIAGEN, Germany),  in accordance to the protocols of the manufacturer (Litekh, Russia).

We revealed that the genetic markers of the severe COVID-19 infection in the Belarusian patients are the heterozygous T/C genotype of the LZTFL1 rs10490770 variant, as well as the A-A haplotype of the ACE2 rs2074192 and rs2285666 loci, and the A-A-C allelic combination of the ACE2 rs2074192, rs2285666 and AGT rs699 genes. Genetic markers associated with mild/moderate severity of COVID-19 were also identified: heterozygous A/C genotype of the AGTR1 rs5186 variant,  G-G-T allelic combination at the ACE2 rs2074192 and rs2285666, AGT rs699 loci (among carriers of these gene variants,  the risk of severe disease is reduced).

The loci of the genes encoding the renin-angiotensin system – ACE2 rs2074192 and rs2285666, AGTR1 rs5186,  and the LZTFL1 rs10490770 genes, as well as allelic combinations between the ACE2 rs2074192, rs2285666 and AGT rs699 loci are informative markers for predicting the severity of COVID-19.

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