FURIN gene variants (rs6224/rs4702) as potential markers of death and cardiovascular traits in severe COVID-19.
Eliecer CotoGuillermo M AlbaicetaLaura Amado-RodríguezMarta García-ClementeElías Cuesta-LlavonaDaniel Vázquez-CotoBelén AlonsoSara IglesiasSantiago MelónMarta E Alvarez-ArgüellesJosé A BogaSusana Rojo-AlbaSergio Pérez-OliveiraVictoria AlvarezJuan GómezPublished in: Journal of medical virology (2022)
Furin is a protease that plays a key role in the infection cycle of SARS-CoV-2 by cleaving the viral proteins during the virus particle assembly. In addition, Furin regulates several physiological processes related to cardio-metabolic traits. DNA variants in the FURIN gene are candidates to regulate the risk of developing these traits as well as the susceptibility to severe COVID-19. We genotyped two functional FURIN variants (rs6224/rs4702) in 428 COVID-19 patients in the intensive care unit. The association with death (N = 106) and hypertension, diabetes, and hyperlipidaemia was statistically evaluated. The risk of death was associated with age, hypertension, and hypercholesterolemia. The two FURIN alleles linked to higher expression (rs6224 T and rs4702 A) were significantly increased in the death cases (odds ratio= 1.40 and 1.43). Homozygosis for the two high expression genotypes (rs6224 TT and rs4702 AA) and for the T-A haplotype was associated with an increased risk of hypercholesterolemia. In the multiple logistic regression both, hypercholesterolemia and the TT + AA genotype were significantly associated with death. In conclusion, besides its association with hypercholesterolemia, FURIN variants might be independent risk factors for the risk of death among COVID-19 patients.
Keyphrases
- sars cov
- copy number
- genome wide
- coronavirus disease
- blood pressure
- respiratory syndrome coronavirus
- type diabetes
- cardiovascular events
- early onset
- gene expression
- dna methylation
- transcription factor
- risk assessment
- skeletal muscle
- insulin resistance
- long non coding rna
- climate change
- cell free
- circulating tumor
- nucleic acid
- human health
- low density lipoprotein