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 rs462574 AA and rs456298 TT genotypes ( p = 0.005 and p = 0.020, respectively), whereas, high heart rate was present in patients with the rs462574 AA 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.