Genetic variants associated with SARS-CoV-2 infection also affect lung function and asthma severity

Area of Science:

• Genetics and Genomics
• Pulmonology
• Infectious Diseases

Background:

• Host genetic factors are implicated in COVID-19 severity.
• Genome-wide association studies identified COVID-19 susceptibility loci near specific genes (SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6, XCR1) and the ABO blood group.
• The association between these genetic factors and lung function/severe asthma requires investigation.

Purpose of the Study:

• To investigate the relationship between polymorphisms in COVID-19 susceptibility genes and lung function/severe asthma.
• To evaluate the role of specific gene variants in asthma phenotypes within a Brazilian population.

Main Methods:

• Genotyping of 784 individuals from the ProAR cohort using the Multi-Ethnic Global Array panel.
• Evaluation of polymorphisms in SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6, XCR1, and the ABO blood-group gene.
• Logistic regression analysis for severe asthma, airway obstruction, and FEV1 reversibility, adjusted for covariates; linkage disequilibrium, haplotype, gene score, and in silico analyses were also performed.

Main Results:

• ABO gene polymorphisms (rs8176733, rs8176725) were associated with increased risk of severe asthma, airway obstruction, and lack of FEV1 reversibility.
• Polymorphisms in CCR9, FYCO1, LZTFL1, and SLC6A20 were identified as risk factors for severe asthma and/or airway obstruction.
• XCR1 polymorphisms showed a protective effect against severe asthma and airway obstruction; a higher number of risk alleles correlated with worse asthma outcomes.

Conclusions:

• Genetic polymorphisms previously associated with respiratory failure in COVID-19 patients are linked to increased susceptibility to severe asthma and reduced lung function in asthmatic individuals.
• These findings highlight shared genetic pathways influencing respiratory health outcomes in both infectious and chronic respiratory diseases.