Association of the Transmembrane Serine Protease-2 (TMPRSS2) Polymorphisms with COVID-19

SARS-CoV-2 uses the ACE2 receptor and the cellular protease TMPRSS2 for entry into target cells. The present study aimed to establish if the TMPRSS2 polymorphisms are associated with COVID-19 disease. The study included 609 patients with COVID-19 confirmed by RT-PCR test and 291 individuals negative for the SARS-CoV-2 infection confirmed by RT-PCR test and without antibodies anti-SARS-CoV-2. Four TMPRSS2 polymorphisms (rs12329760, rs2298659, rs456298, and rs462574) were determined using the 5'exonuclease TaqMan assays. Under different inheritance models, the rs2298659 (p_codominant2 = 0.018, p_recessive = 0.006, p_additive = 0.019), rs456298 (p_codominant1 = 0.014, p_codominant2 = 0.004; p_dominant = 0.009, p_recessive = 0.004, p_additive = 0.0009), and rs462574 (p_codominant1 = 0.017, p_codominant2 = 0.004, p_dominant = 0.041, p_recessive = 0.002, p_additive = 0.003) polymorphisms were associated with high risk of developing COVID-19. Two risks (ATGC and GAAC) and two protectives (GAGC and GAGT) haplotypes were detected. High levels of lactic acid dehydrogenase (LDH) were observed in patients with the rs462574AA and rs456298TT genotypes (p = 0.005 and p = 0.020, respectively), whereas, high heart rate was present in patients with the rs462574AA genotype (p = 0.028). Our data suggest that the rs2298659, rs456298, and rs462574 polymorphisms independently and as haplotypes are associated with the risk of COVID-19. The rs456298 and rs462574 genotypes are related to high levels of LDH and heart rate.