Dataset Information

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

ABSTRACT:

Objectives

To assess associations between the functional polymorphisms G-2518A at the chemokine (C-C motif) ligand 2 gene (CCL2) and mannose binding lectin (MBL) codon 54 variant (A/B) and susceptibility to SARS.

Methods

We genotyped the CCL2 G-2518A and MBL codon 54 variant (A/B) in 4 case-control populations of Chinese descent, totally consisting of 932 patients with SARS and 982 control subjects.

Results

Both the high-CCL2-producing GG genotype and the low-MBL-producing B allele were consistently associated with increased risks of SARS-CoV infection in all 4 case-control populations (joint P = 1.6 × 10(-4) and 4.9 × 10(-8), for CCL2 and MBL respectively), with no interaction between polymorphisms could be detected. Furthermore, all the 4 case-control studies demonstrated a cumulative effect on risk of SARS-CoV infection for the combination of polymorphisms (joint P = 1.3 × 10(-10)). However, tests using the area under the curve (AUC) indicated that at this stage, the polymorphisms were unlikely to be appropriate for risk prediction testing because of low AUC values (all <66%). Additionally, no association was observed between the polymorphisms and severity of SARS.

Conclusions

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

SUBMITTER: Tu X

PROVIDER: S-EPMC7112636 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Publications

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

Tu Xinyi X Chong Wai Po WP Zhai Yun Y Zhang Hongxing H Zhang Fang F Wang Shixin S Liu Wei W Wei Maoti M Siu Nora Ho On NH Yang Hao H Yang Wanling W Cao Wuchun W Lau Yu Lung YL He Fuchu F Zhou Gangqiao G

The Journal of infection 20150327 1

<h4>Objectives</h4>To assess associations between the functional polymorphisms G-2518A at the chemokine (C-C motif) ligand 2 gene (CCL2) and mannose binding lectin (MBL) codon 54 variant (A/B) and susceptibility to SARS.<h4>Methods</h4>We genotyped the CCL2 G-2518A and MBL codon 54 variant (A/B) in 4 case-control populations of Chinese descent, totally consisting of 932 patients with SARS and 982 control subjects.<h4>Results</h4>Both the high-CCL2-producing GG genotype and the low-MBL-producing ...[more]

PMID: 25818534

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Project description:Genetic variability across the three major histocompatibility complex (MHC) class I genes (human leukocyte antigen A [HLA-A], -B, and -C genes) may affect susceptibility to and severity of the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). We performed a comprehensive in silico analysis of viral peptide-MHC class I binding affinity across 145 HLA-A, -B, and -C genotypes for all SARS-CoV-2 peptides. We further explored the potential for cross-protective immunity conferred by prior exposure to four common human coronaviruses. The SARS-CoV-2 proteome was successfully sampled and was represented by a diversity of HLA alleles. However, we found that HLA-B*46:01 had the fewest predicted binding peptides for SARS-CoV-2, suggesting that individuals with this allele may be particularly vulnerable to COVID-19, as they were previously shown to be for SARS (M. Lin, H.-T. Tseng, J. A. Trejaut, H.-L. Lee, et al., BMC Med Genet 4:9, 2003, https://bmcmedgenet.biomedcentral.com/articles/10.1186/1471-2350-4-9). Conversely, we found that HLA-B*15:03 showed the greatest capacity to present highly conserved SARS-CoV-2 peptides that are shared among common human coronaviruses, suggesting that it could enable cross-protective T-cell-based immunity. Finally, we reported global distributions of HLA types with potential epidemiological ramifications in the setting of the current pandemic.IMPORTANCE Individual genetic variation may help to explain different immune responses to a virus across a population. In particular, understanding how variation in HLA may affect the course of COVID-19 could help identify individuals at higher risk from the disease. HLA typing can be fast and inexpensive. Pairing HLA typing with COVID-19 testing where feasible could improve assessment of severity of viral disease in the population. Following the development of a vaccine against SARS-CoV-2, the virus that causes COVID-19, individuals with high-risk HLA types could be prioritized for vaccination.

Dataset Information

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

Objectives

Methods

Results

Conclusions

Publications

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

Similar Datasets

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