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

Rebeca I Montero ¹ Cinthia Dionicio ^1,2 Gino Noris ¹ Maricela Piña-Pozas ³ Carla Santana ^1* ROCIO GOMEZ ^4*

• ¹ Biología Molecular Diagnóstica, Querétaro, Qro., Mexico
• ² Jurisdicción Sanitaria 02, Secretaría de Salud, Iguala, Gro., Mexico
• ³ Centro de Investigación en Salud Poblacional, INSP, Mexico City, Mexico
• ⁴ Department of Toxicology, Center for Research and Advanced Studies of the National Polytechnic Institute, Mexico City, México, Mexico

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 found 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.