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

J Infect. 2015 Jul;71(1):101-9. doi: 10.1016/j.jinf.2015.03.006. Epub 2015 Mar 27.

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.

Keywords: CCL2; MBL; Polymorphism; Severe acute respiratory syndrome; Susceptibility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Asian Continental Ancestry Group
  • Case-Control Studies
  • Chemokine CCL2 / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Male
  • Mannose-Binding Lectin / genetics*
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Severe Acute Respiratory Syndrome / epidemiology*
  • Severe Acute Respiratory Syndrome / genetics*
  • Young Adult

Substances

  • CCL2 protein, human
  • Chemokine CCL2
  • Mannose-Binding Lectin