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Association of Interleukin-6-572C/G Gene Polymorphism and Serum or Cerebrospinal Fluid Interleukin-6 Level with Enterovirus 71 Encephalitis in Chinese Han Patients with Hand, Foot, and Mouth Disease

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Abstract

Interleukin-6 (IL-6), as one of pro-inflammatory cytokines, plays a key role in Enterovirus 71 (EV71) encephalitis. We investigated the association of IL-6-572C/G polymorphism and serum or cerebrospinal fluid (CSF) IL-6 level with EV71 encephalitis in patients with hand, foot, and mouth disease (HFMD). This study was carried out in 59 Chinese Han patients with EV71 encephalitis, 128 EV71-related HFMD without complications, and 232 controls. The IL-6-572C/G polymorphism was detected by polymerase chain reaction-restricted fragment length polymorphism gene analysis. Serum or CSF IL-6 levels were determined using a commercial enzyme-linked immunosorbent assay. The patients with EV71 encephalitis had a higher frequency of IL-6-572GG/GC genotype compared to the patients with EV71-related HFMD without encephalitis complications (40.7 vs. 15.6 %, odds ratio (OR) = 3.70, 95 % confidence interval (CI) = 1.83–7.50, p = 0.001). Similarly, the frequency of IL-6-572 G allele among the patients with EV71 encephalitis was also higher than that of patients with EV71-related HFMD without encephalitis complications (23.7 vs. 8.6 %, OR = 3.31, 95 % CI = 1.80–6.08, p < 0.001). Serum IL-6 levels in G carries (CG + GG) (195.1 ± 11.8 pg/ml) elevated significantly compared to CC homozygotes (167.7 ± 6.7 pg/ml) in EV71-infected patients (p < 0.001), but no significant differences were observed in CSF IL-6 levels among different genotypes in patients with EV71 encephalitis. Furthermore, G carriers (GG + GC) (10.6 ± 1.29 mg/l) had significantly higher blood CRP levels compared to CC homozygotes (9.31 ± 1.93 mg/l) in patients with EV71 encephalitis (p = 0.005). These findings suggested that IL-6-572 G allele was significantly associated with the susceptibility to EV71 encephalitis in Chinese Han patients, and IL-6-572 G allele might elevate the risk to EV71 encephalitis.

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Acknowledgments

Financial support for this project was supported by grants from the Natural Science of China (no. 31171212), and there are no ethical/legal conflicts involved in the article.

Conflict of Interest

The authors declared no competing of interests.

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Authors and Affiliations

  1. Department of Neurology & Rehabilitation, The Affiliated Women & Children Hospital of Qingdao University Medical School, 6 Tongfu Road, Qingdao, 266034 , Shandong, China

    Aiyun Yuan, Mei Hou & **ju Wang

  2. Pediatric Department, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003 , Shandong, China

    Aiyun Yuan, Jian Li, Peipei Liu, Zongbo Chen, **ju Wang & Zhenliang Han

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Correspondence to Zongbo Chen.

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Yuan, A., Li, J., Liu, P. et al. Association of Interleukin-6-572C/G Gene Polymorphism and Serum or Cerebrospinal Fluid Interleukin-6 Level with Enterovirus 71 Encephalitis in Chinese Han Patients with Hand, Foot, and Mouth Disease. Inflammation 38, 728–735 (2015). https://doi.org/10.1007/s10753-014-9983-1

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