Functional polymorphisms of the CCL2 and MBL genes cumulatively increase susceptibility to severe acute respiratory syndrome coronavirus infection - 04/06/15

Doi : 10.1016/j.jinf.2015.03.006

Xinyi Tu ^a,^b,^f,^g,^{^{h
X.T., W.P.C., Y.Z., and H.Z. contributed equally to the study. The School of Life Sciences, Tsinghua University, and the State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine contributed equally to this work.}}, Wai Po Chong ^c,^{^{h
X.T., W.P.C., Y.Z., and H.Z. contributed equally to the study. The School of Life Sciences, Tsinghua University, and the State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine contributed equally to this work.}}, Yun Zhai ^b,^f,^g,^{^{h
X.T., W.P.C., Y.Z., and H.Z. contributed equally to the study. The School of Life Sciences, Tsinghua University, and the State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine contributed equally to this work.}}, Hongxing Zhang ^b,^f,^g,^{^{h
X.T., W.P.C., Y.Z., and H.Z. contributed equally to the study. The School of Life Sciences, Tsinghua University, and the State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine contributed equally to this work.}}, Fang Zhang ^d, Shixin Wang ^e, Wei Liu ^d, Maoti Wei ^e, Nora Ho On Siu ^c, Hao Yang ^b,^f,^g, Wanling Yang ^c, Wuchun Cao ^d, Yu Lung Lau ^c,^⁎,^{^{i
G.Z., F.H., and Y.L.L. contributed equally to the study, should be considered as joint corresponding authors.}} , Fuchu He ^a,^b,^f,^g,^⁎,^{^{i
G.Z., F.H., and Y.L.L. contributed equally to the study, should be considered as joint corresponding authors.}} , Gangqiao Zhou ^b,^f,^g,^⁎,^{^{i
G.Z., F.H., and Y.L.L. contributed equally to the study, should be considered as joint corresponding authors.}}
^a School of Life Sciences, Tsinghua University, Beijing, China
^b The State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China
^c Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
^d The State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China
^e Wujing Medical College at Tianjin, Tianjin, China
^f National Engineering Research Center for Protein Drugs, Beijing, China
^g National Center for Protein Science at Beijing, Beijing, China

^∗Corresponding author. The State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing, 100850, China. Tel.: +86 10 66930490.^∗∗Corresponding author. The State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing, 100850, China. Tel.: +86 10 68177417.^∗∗∗Corresponding author. Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China. Tel.: +86 852 2255 4481.

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Summary

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.

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Highlights

•	This study includes the largest cohort in genetic association studies of SARS.
•	The GG genotype at CCL2 G-2518A was associated with an increased risk of SARS-CoV infection.
•	The MBL B allele was associated with an increased risk of SARS-CoV infection.
•	SNPs of CCL2 and MBL cumulatively increase susceptibility to SARS-CoV infection.
•	The joint population attributable fraction (PAF) for these two SNPs is 28.5%.

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Keywords : CCL2, MBL, Severe acute respiratory syndrome, Polymorphism, Susceptibility

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Vol 71 - N° 1

P. 101-109 - juillet 2015 Retour au numéro

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Functional polymorphisms of the CCL2 and MBL genes cumulatively increase susceptibility to severe acute respiratory syndrome coronavirus infection - 04/06/15

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