# Genetic variants in TMPRSS2 influence SARS-CoV-2 infection susceptibility within Mexican Mestizos

## TL;DR

This study finds that genetic variants in the TMPRSS2 gene are linked to a higher risk of SARS-CoV-2 infection in Mexican Mestizos.

## Contribution

The study identifies specific TMPRSS2 genetic variants and haplotypes associated with increased SARS-CoV-2 infection risk in a Mexican Mestizo population.

## Key findings

- Three TMPRSS2 SNPs (rs75603675, rs4303795, rs8134378) significantly increase SARS-CoV-2 infection risk.
- Haplotypes CAG, AGA, and AGG in TMPRSS2 are strongly associated with higher infection susceptibility.
- Risk alleles and haplotypes were more common in infected individuals, increasing risk by at least twofold.

## Abstract

Since host genetics is one of the primary factors contributing to COVID-19 susceptibility and its clinical progression, several studies have focused on analysing the implications of genetic polymorphisms associated with COVID-19. These studies particularly emphasise on common variants in genes that are involved in the viral mechanism of host entry and in the host’s response to infection. In this study, we explored the participation of 24 single nucleotide polymorphisms located on the ACE, ADAM17, FURIN, IFITM3, TMPRSS2 and VDR genes in SARS-CoV-2 infection susceptibility. Three of these SNPs in TMPRSS2 (rs75603675, OR = 1.86, 95%CI = 1.29–2.66, p ≤ 0.001; rs4303795, OR = 1.98, 95%CI = 1.38–2.84, p ≤ 0.001 and rs8134378, OR = 2.59, 95%CI = 1.28–5.21, p ≤ 0.01) had a significant association with an increased risk of infection. When comparing haplotype frequency distributions, the haplotypes CAG (OR = 7.34, 95%CI = 5.51–9.77), AGA (OR = 2.46, 95%CI = 1.12–5.44), and AGG (OR = 1.59, 95%CI = 1.17–2.16) presented significant associations, suggesting that TMPRSS2 influences SARS-CoV-2 infection susceptibility within Mexican Mestizos. These risk alleles and their haplotypes were found more frequently in the case group than in the reference group, contributing to at least a twofold increase in the risk of SARS-CoV-2 infection, a finding that was reinforced by meta-analyses.