Functional polymorphisms of the CCL2 and MBL genes cumulatively increase susceptibility to severe acute respiratory syndrome coronavirus infection

Abstract

The CCL2 G-2518A and MBL codon 54 variant have a significantly cumulative effect on increased risk of SARS-CoV infection.

IFITM3, TLR3, and CD55 Gene SNPs and Cumulative Genetic Risks for Severe Outcomes in Chinese Patients With H7N9/H1N1pdm09 Influenza

“…The death risk was shown to be incremental in GRS analysis (aHR 3.5, per risk genotype); the presence of both genotypes conferred an almost 10-fold higher risk than those with neither. These results strongly suggest that a combination of host genetic factors ("genetic background") may influence the clinical course and outcomes of influenza, along with known clinical and virologic factors [7,8,9,41,42]. Our list of candidate genes/SNPs is not exhaustive; as experimental and genome-wide association studies continue to uncover these determinants, more variables/ combinations, including those related to adaptive immunity are expected to be considered in genetic risk evaluation in severe influenza [7,8,9,10,21,25,43,44].…”

“…D222G, H275Y, and R292K mutations should have a minimal impact on results because of their reported rarity [25,28,29,31,35]. The effects on host susceptibility to initial infection (compared with uninfected patients) [14,15,20,26], vaccine response, and the reasons why these immune-related genetic variants (thus implicated in infective/noninfective inflammatory diseases) are selected and gained prevalence among the Asian populations should warrant investigation [15,19,37,38,42,43,45]. Studies on seasonal influenza where preexisting immunity may exist, and other potential genetic determinants for influenza severity are in progress.…”

Molecular immune pathogenesis and diagnosis of COVID-19

“…In MERS-CoV infection, MHC II molecules, such as HLA-DRB1*11:01 and HLA-DQB1*02:0, are associated with the susceptibility to MERS-CoV infection [28]. Besides, gene polymorphisms of MBL (mannose-binding lectin) associated with antigen presentation are related to the risk of SARS-CoV infection [29]. These researches will provide valuable clues for the prevention, treatment, and mechanism of COVID-19.…”

Host Genetic Variants Potentially Associated With SARS-CoV-2: A Multi-Population Analysis

“…Carriers of the T allele had lower AHSG serum concentration and increased risk of SARS illness ( Zhu et al, 2011 ). Low levels of the Mannose-binding lectin (MBL), another key molecule in innate immunity, caused by a missense variant (rs1800450), was also linked to increased SARS-CoV-1 susceptibility ( Tu et al, 2015 ). Similarly, a functional polymorphism of the chemokine (C–C motif) ligand 2 ( CCL2 ) gene (rs1024611) was associated with an increased risk of SARS-CoV-1 infection ( Tu et al, 2015 ).…”

“…Low levels of the Mannose-binding lectin (MBL), another key molecule in innate immunity, caused by a missense variant (rs1800450), was also linked to increased SARS-CoV-1 susceptibility ( Tu et al, 2015 ). Similarly, a functional polymorphism of the chemokine (C–C motif) ligand 2 ( CCL2 ) gene (rs1024611) was associated with an increased risk of SARS-CoV-1 infection ( Tu et al, 2015 ). CCL2 belongs to the chemokines family, and plays a vital role in immune cells trafficking during SARS-CoV-1 infection ( Law et al, 2005 ).…”