title: Functional polymorphisms of the CCL2 and MBL genes cumulatively increase susceptibility to severe acute respiratory syndrome coronavirus infection.
abstract: OBJECTIVE
  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.
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing, China; The State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China; National Engineering Research Center for Protein Drugs, Beijing, China; National Center for Protein Science at Beijing, Beijing, China.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Tu
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
authors.forename: Wai Po
authors.initials: WP
authors.lastname: Chong
authors.affiliation: The State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China; National Engineering Research Center for Protein Drugs, Beijing, China; National Center for Protein Science at Beijing, Beijing, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhai
authors.affiliation: The State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China; National Engineering Research Center for Protein Drugs, Beijing, China; National Center for Protein Science at Beijing, Beijing, China.
authors.forename: Hongxing
authors.initials: H
authors.lastname: Zhang
authors.affiliation: The State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Wujing Medical College at Tianjin, Tianjin, China.
authors.forename: Shixin
authors.initials: S
authors.lastname: Wang
authors.affiliation: The State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Wujing Medical College at Tianjin, Tianjin, China.
authors.forename: Maoti
authors.initials: M
authors.lastname: Wei
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
authors.forename: Nora Ho On
authors.initials: NH
authors.lastname: Siu
authors.affiliation: The State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China; National Engineering Research Center for Protein Drugs, Beijing, China; National Center for Protein Science at Beijing, Beijing, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
authors.forename: Wanling
authors.initials: W
authors.lastname: Yang
authors.affiliation: The State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Wuchun
authors.initials: W
authors.lastname: Cao
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China. Electronic address: lauylung@hkucc.hku.hk.
authors.forename: Yu Lung
authors.initials: YL
authors.lastname: Lau
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing, China; The State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China; National Engineering Research Center for Protein Drugs, Beijing, China; National Center for Protein Science at Beijing, Beijing, China. Electronic address: hefc@nic.bmi.ac.cn.
authors.forename: Fuchu
authors.initials: F
authors.lastname: He
authors.affiliation: The State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China; National Engineering Research Center for Protein Drugs, Beijing, China; National Center for Protein Science at Beijing, Beijing, China. Electronic address: zhougq114@126.com.
authors.forename: Gangqiao
authors.initials: G
authors.lastname: Zhou
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D045169:Severe Acute Respiratory Syndrome / Q000453:epidemiology* / Q000235:genetics*; D055815:Young Adult
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D037601:Mannose-Binding Lectin
keywords: CCL2; MBL; Polymorphism; Severe acute respiratory syndrome; Susceptibility
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