Mannose binding lectin gene 2 (rs1800450) missense variant may contribute to development and severity of COVID-19 infection

Infect Genet Evol. 2021 Apr:89:104717. doi: 10.1016/j.meegid.2021.104717. Epub 2021 Jan 27.

Abstract

Background/objectives: COVID-19 followed a mortal course in some young patients without any underlying factors, however, it followed a very benign course in some very older individuals with multiple comorbidities. These observations question if some genetic factors may be related to the vulnerability and poor prognosis of the disease. In this study, we aimed to investigate whether MBL2 gene B variant at codon 54 (rs1800450) were related to the variabilities in clinical course of this infection.

Methods: 284 PCR-confirmed COVID-19 patients and 100 healthy controls were included in the study. COVID-19 patients were subdivided according to the clinical features and clinical characteristics were analyzed. DNAs of all patients and controls were examined for the codon 54 A/B (gly54asp: rs1800450) variation in exon 1 of the MBL2 gene.

Results: In univariate analysis, BB genotype of MBL2 gene was more common among COVID-19 cases compared with controls (10.9% vs 1.0%, respectively; OR = 12.1, 95%CI = 1.6-90.1, p = 0.001). Multivariate analyses, adjusted for age, sex and MBL genetic variants, revealed that when compared with the COVID-19 patients that had AA genotype (reference), the patients that had BB or AB genotypes suffered from a higher risk for severe disease (for BB genotype, odds ratio (OR) = 5.3, p < 0.001; for AB genotype, OR = 2.9, p = 0.001) and for ICU need (for BB genotype, OR = 19.6, p < 0.001; for AB genotype, OR = 6.9, p = 0.001). On the other hand, there was not any significant difference between the genotype variants in terms of mortality at 28 days or development of secondary bacterial infection.

Conclusion: The B variants of MBL2 gene at codon 54, which were associated with lower MBL2 levels, were related to a higher risk for a more severe clinical course of COVID-19 infection in some respects. Our findings may have potential future implications, e.g. for use of MBL protein as potential therapeutics or prioritize the individuals with B variants during vaccination strategies.

Keywords: COVID-19; Cytokine; Gene mutation; Hyperinflammation; MBL2; SARS-CoV-2.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • COVID-19 / genetics*
  • COVID-19 / pathology*
  • COVID-19 / virology
  • Case-Control Studies
  • Comorbidity
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Mannose-Binding Lectin / genetics*
  • Mannose-Binding Lectin / metabolism
  • Middle Aged
  • Mutation, Missense*
  • Protein Interaction Maps
  • SARS-CoV-2 / isolation & purification
  • Severity of Illness Index
  • Young Adult

Substances

  • MBL2 protein, human
  • Mannose-Binding Lectin