Implication of myddosome complex genetic variants in outcome severity of COVID-19 patients.

Abstract

BACKGROUND/PURPOSE(S):

During a viral infection, the immune response is mediated by the toll-like receptors and myeloid differentiation Factor 88 (MyD88) that play an important role sensing infections such as SARS-CoV-2 which has claimed the lives of more than 6.8 million people around the world.

METHODS:

We carried out a cross-sectional with a population of 618 SARS-CoV-2-positive unvaccinated subjects and further classified based on severity: 22% were mild, 34% were severe, 26% were critical, and 18% were deceased. Toll Like Receptor 7 (TLR7) single-nucleotide polymorphisms (rs3853839, rs179008, rs179009, and rs2302267) and MyD88 (rs7744) were genotyped using TaqMan OpenArray. The association of polymorphisms with disease outcomes was performed by logistic regression analysis adjusted by covariates.

RESULTS:

A significant association of rs3853839 and rs7744 of the TLR7 and MyD88 genes, respectively, was found with COVID-19 severity. The G/G genotype of the rs3853839 TLR7 was associated with the critical outcome showing an Odd Ratio = 1.98 (95% IC = 1.04-3.77). The results highlighted an association of the G allele of MyD88 gene with severe, critical and deceased outcomes. Furthermore, in the dominant model (AG + GG vs. AA), we observed an Odd Ratio = 1.70 (95% CI = 1.02-2.86) with severe, Odd Ratio = 1.82 (95% CI = 1.04-3.21) with critical, and Odd Ratio = 2.44 (95% CI = 1.21-4.9) with deceased outcomes.

CONCLUSION:

To our knowledge this work represents an innovative report that highlights the significant association of TLR7 and MyD88 gene polymorphisms with COVID-19 outcomes and the possible implication of the MyD88 variant with D-dimer and IFN-α concentrations.

• Authors: Laura E Martínez-Gómez, Carlos Martinez-Armenta, Daniel Medina-Luna, María Luisa Ordoñez-Sánchez, Tere Tusie-Luna, Silvestre Ortega-Peña, Brígida Herrera-López, Carlos Suarez-Ahedo, Guadalupe Elizabeth Jimenez-Gutierrez, Alberto Hidalgo-Bravo, Paola Vázquez-Cárdenas, Rosa P Vidal-Vázquez, Juan P Ramírez-Hinojosa, Pilar Miyoko Martinez Matsumoto, Gilberto Vargas-Alarcón, Rosalinda Posadas-Sánchez, José-Manuel Fragoso, Felipe de J Martínez-Ruiz, Dulce M Zayago-Angeles, Mónica Maribel Mata-Miranda, Gustavo Jesús Vázquez-Zapién, Adriana Martínez-Cuazitl, Javier Andrade-Alvarado, Julio Granados, Luis Ramos-Tavera, María Del Carmen Camacho-Rea, Yayoi Segura-Kato, José Manuel Rodríguez-Pérez, Roberto Coronado-Zarco, Rafael Franco-Cendejas, Luis Esau López-Jácome, Jonathan J Magaña, Marcela Vela-Amieva, Carlos Pineda, Gabriela Angélica Martínez-Nava, Alberto López-Reyes
• Journal: Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi (J Microbiol Immunol Infect) Vol. 56 Issue 5 Pg. 939-950 (Oct 2023) ISSN: 1995-9133 [Electronic] England
• PMID: 37365052 (Publication Type: Journal Article)
• Copyright: Copyright © 2023. Published by Elsevier B.V.

Chemical References

• Toll-Like Receptor 7
• Myeloid Differentiation Factor 88

Topics

• Humans
• Toll-Like Receptor 7 (genetics, metabolism)
• Genetic Predisposition to Disease
• Myeloid Differentiation Factor 88 (genetics)
• Cross-Sectional Studies
• COVID-19 (genetics)
• SARS-CoV-2
• Genotype
• Polymorphism, Single Nucleotide (genetics)