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Association of TLR8 Variants in Sex-Based Clinical Differences in Patients with COVID-19

  • María del Carmen Camacho-Rea,
  • Laura Edith Martínez-Gómez,
  • Carlos Martinez-Armenta,
  • Gabriela Angélica Martínez-Nava,
  • Silvestre Ortega-Peña,
  • Jessel Olea-Torres,
  • Brígida Herrera-López,
  • Carlos Suarez-Ahedo,
  • Paola Vázquez-Cárdenas,
  • Rosa P. Vidal-Vázquez,
  • Juan Pablo Ramírez-Hinojosa,
  • Gilberto Vargas-Alarcón,
  • Rosalinda Posadas-Sánchez,
  • José Manuel Fragoso,
  • Felipe De Jesús Martínez-Ruiz,
  • Dulce María Zayago-Angeles,
  • Mónica Maribel Mata-Miranda,
  • Gustavo Jesús Vazquez-Zapien,
  • Adriana Martínez-Cuazitl,
  • Armando Garcia-Galicia,
  • Julio Granados,
  • Luis Ramos,
  • José Manuel Rodríguez-Pérez,
  • Carlos Pineda,
  • Alberto López-Reyes

摘要

The host immune response might confer differential vulnerability to SARS‐CoV‐2 infection. The Toll-like receptor 8 (TLR8), could participated for severe COVID-19 outcomes. To investigated the relationship of TLR8 rs3764879-C/G, rs3764880-A/G, and rs3761624-A/G with COVID‐19 outcomes and with biochemical parameters. A cross-sectional study of 830 laboratory‐confirmed COVID‐19 patients was performed, and classified into mild, severe, critical, and deceased outcomes. The TLR8 rs3764879-C/G, rs3764880-A/G, and rs3761624-A/G polymorphisms were genotyped. A logistic regression analysis was performed to determinate the association with COVID‐19. A stratified analysis was by alleles was done with clinical and metabolic markets. In all outcomes, men presented the highest ferritin levels compared to women (P < 0.001). LDH levels were significantly different between sex in mild (P = 0.003), severe (P < 0.001) and deceased (P = 0.01) COVID-19 outcomes. The GGG haplotype showed an Odds Ratio of 1.55 (Interval Confidence 95% 1.05–2.32; P = 0.03) in men. Among patients with severe outcome, we observed that the carriers of the GGG haplotype had lower Ferritin, C-reactive protein and LDH levels than the CAA carriers (P < 0.01). After further stratified by sex, these associations were also seen in the male patients, except for D-dimer. Interestingly, among men patients, we could observe associations between TLR8 haplotypes and Ferritin (P < 0.001), D-dimer (P = 0.04), C-reactive protein, and Lactate dehydrogenase in mild (P = 0.04) group. Our results suggest that even though TLR8 haplotypes show a significant association with COVID-19 outcomes, they are associated with clinical markers in COVID-19 severity.