Association of Chemotactic Chemokine Ligand 5 Polymorphisms with the Risk of Developing Severe Enterovirus 71 Infection

Mao-zhong Li National Institute for Viral Disease Control and Prevention, China CDC, Key Laboratory for Medical Virology, National Health and Family Planning Commission, Beijing, China; Ji'nan Municipal Center for Disease Control and Prevention, Ji'nan, China; National Center for Public Health Surveillance and Information Services, Chinese Center for Disease Control and Prevention, Beijing, China; Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China; Nanjing Children's Hospital, Medical School of Nanjing University, Nanjing, China

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Li-li Pang National Institute for Viral Disease Control and Prevention, China CDC, Key Laboratory for Medical Virology, National Health and Family Planning Commission, Beijing, China; Ji'nan Municipal Center for Disease Control and Prevention, Ji'nan, China; National Center for Public Health Surveillance and Information Services, Chinese Center for Disease Control and Prevention, Beijing, China; Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China; Nanjing Children's Hospital, Medical School of Nanjing University, Nanjing, China

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Ai-ying Bai National Institute for Viral Disease Control and Prevention, China CDC, Key Laboratory for Medical Virology, National Health and Family Planning Commission, Beijing, China; Ji'nan Municipal Center for Disease Control and Prevention, Ji'nan, China; National Center for Public Health Surveillance and Information Services, Chinese Center for Disease Control and Prevention, Beijing, China; Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China; Nanjing Children's Hospital, Medical School of Nanjing University, Nanjing, China

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Shi-cheng Yu National Institute for Viral Disease Control and Prevention, China CDC, Key Laboratory for Medical Virology, National Health and Family Planning Commission, Beijing, China; Ji'nan Municipal Center for Disease Control and Prevention, Ji'nan, China; National Center for Public Health Surveillance and Information Services, Chinese Center for Disease Control and Prevention, Beijing, China; Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China; Nanjing Children's Hospital, Medical School of Nanjing University, Nanjing, China

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Xun Gong National Institute for Viral Disease Control and Prevention, China CDC, Key Laboratory for Medical Virology, National Health and Family Planning Commission, Beijing, China; Ji'nan Municipal Center for Disease Control and Prevention, Ji'nan, China; National Center for Public Health Surveillance and Information Services, Chinese Center for Disease Control and Prevention, Beijing, China; Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China; Nanjing Children's Hospital, Medical School of Nanjing University, Nanjing, China

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Na Liu National Institute for Viral Disease Control and Prevention, China CDC, Key Laboratory for Medical Virology, National Health and Family Planning Commission, Beijing, China; Ji'nan Municipal Center for Disease Control and Prevention, Ji'nan, China; National Center for Public Health Surveillance and Information Services, Chinese Center for Disease Control and Prevention, Beijing, China; Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China; Nanjing Children's Hospital, Medical School of Nanjing University, Nanjing, China

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Kun Cai National Institute for Viral Disease Control and Prevention, China CDC, Key Laboratory for Medical Virology, National Health and Family Planning Commission, Beijing, China; Ji'nan Municipal Center for Disease Control and Prevention, Ji'nan, China; National Center for Public Health Surveillance and Information Services, Chinese Center for Disease Control and Prevention, Beijing, China; Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China; Nanjing Children's Hospital, Medical School of Nanjing University, Nanjing, China

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Guang-cheng Xie National Institute for Viral Disease Control and Prevention, China CDC, Key Laboratory for Medical Virology, National Health and Family Planning Commission, Beijing, China; Ji'nan Municipal Center for Disease Control and Prevention, Ji'nan, China; National Center for Public Health Surveillance and Information Services, Chinese Center for Disease Control and Prevention, Beijing, China; Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China; Nanjing Children's Hospital, Medical School of Nanjing University, Nanjing, China

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Wen-juan Gao National Institute for Viral Disease Control and Prevention, China CDC, Key Laboratory for Medical Virology, National Health and Family Planning Commission, Beijing, China; Ji'nan Municipal Center for Disease Control and Prevention, Ji'nan, China; National Center for Public Health Surveillance and Information Services, Chinese Center for Disease Control and Prevention, Beijing, China; Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China; Nanjing Children's Hospital, Medical School of Nanjing University, Nanjing, China

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Yu Jin National Institute for Viral Disease Control and Prevention, China CDC, Key Laboratory for Medical Virology, National Health and Family Planning Commission, Beijing, China; Ji'nan Municipal Center for Disease Control and Prevention, Ji'nan, China; National Center for Public Health Surveillance and Information Services, Chinese Center for Disease Control and Prevention, Beijing, China; Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China; Nanjing Children's Hospital, Medical School of Nanjing University, Nanjing, China

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Zhao-jun Duan National Institute for Viral Disease Control and Prevention, China CDC, Key Laboratory for Medical Virology, National Health and Family Planning Commission, Beijing, China; Ji'nan Municipal Center for Disease Control and Prevention, Ji'nan, China; National Center for Public Health Surveillance and Information Services, Chinese Center for Disease Control and Prevention, Beijing, China; Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China; Nanjing Children's Hospital, Medical School of Nanjing University, Nanjing, China

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Respiratory damage is a main manifestation of severe Enterovirus 71 (EV71) infection. Polymorphisms of -403G/A (rs2107538), -28C/G (rs2280788), and In1.1T/C (rs2280789) in chemotactic chemokine ligand 5 (CCL5) have linked with many respiratory diseases. In this study, we explored the possible correlation of CCL5 polymorphisms with severe EV71 infection. Blood samples were obtained from 87 children hospitalized for EV71 infection. Fifty-seven healthy children were enrolled as asymptomatic controls. Genotype and allele frequencies were analyzed by logistic regression analysis. There were statistically significant differences in polymorphisms of CCL5 -403G/A and In1.1T/C for dominant model (P = 0.016; P = 0.027) and additive model (P = 0.010; P = 0.019) between patients with severe EV71 infection and asymptomatic controls. With ordinal logistic regression model analysis, statistically significant differences were found between polymorphisms of CCL5 (-403G/A) (P = 0.034) with the severity of EV71 infection after adjusting for age. The frequency of A-C-C haplotype was significantly higher in EV71 infection patients than controls (P = 0.032). These results suggest that CCL5 -403G/A and In1.1T/C polymorphisms may contribute to severe EV71 infection and individuals with haplotype of A-C-C may exhibit higher risk of developing severe EV71 infection. These findings may provide insights into pathogenic and protective mechanisms of severe EV71 infection.

Author Notes

* Address correspondence to Zhao-jun Duan, Department of Viral Diarrhea, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chang-Bai Rd 155, Beijing 102206, People's Republic of China, E-mail: zhaojund@126.com or Yu Jin, Department of Gastroenterology, Nanjing Children's Hospital, Medical School of Nanjing University, Nanjing 210093, People's Republic of China, E-mail: jinyuldyy@163.com.
† These authors contributed equally to this work.

Financial support: The work was supported by China Mega-Project for Infectious Disease (grant no. 2014ZX10004002-004) and China Mega-Project for Infectious Disease (grant no. 2011ZX10004-001).

Authors' addresses: Mao-zhong Li, Li-li Pang, Na Liu, Kun Cai, Guang-cheng Xie, Wen-juan Gao, and Zhao-jun Duan, Department of Viral Diarrhea, National Institute for Viral Disease Control and Prevention, Beijing, China, E-mails: maozhonglee@163.com, cactusea@163.com, unali@163.com, 382068374@qq.com, xieguangcheng123@126.com, gaowj828@126.com, and zhaojund@126.com. Ai-ying Bai, Ji'nan Municipal Center for Disease Control and Prevention, Ji'nan, China, E-mail: baiaiying111@163.com. Shi-cheng Yu, National Center for Public Health Surveillance and Information Services, Chinese Center for Disease Control and Prevention, Beijing, China, E-mail: shicheng_yu@hotmail.com. Xun Gong, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China, E-mail: gongxun8269@163.com. Yu Jin, Department of Gastroenterology, Nanjing Children's Hospital, Medical School of Nanjing University, Nanjing, China, E-mail: jinyuldyy@163.com.

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