Polymorphisms in enterovirus 71 receptors associated with susceptibility and clinical severity

Ting-Yu Yen; Wei-Liang Shih; Yi-Chuan Huang; Jian-Te Lee; Li-Min Huang; Luan-Yin Chang

doi:10.1371/journal.pone.0206769

Polymorphisms in enterovirus 71 receptors associated with susceptibility and clinical severity

PLoS One. 2018 Nov 5;13(11):e0206769. doi: 10.1371/journal.pone.0206769. eCollection 2018.

Authors

Ting-Yu Yen¹, Wei-Liang Shih², Yi-Chuan Huang³, Jian-Te Lee⁴, Li-Min Huang⁵, Luan-Yin Chang⁵

Affiliations

¹ Department of Pediatrics, China Medical University Children's Hospital, China Medical University, Taichung, Taiwan.
² Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
³ Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
⁴ Department of Pediatrics, National Taiwan University Hospital, Yun-Lin Branch, Yunlin, Taiwan.
⁵ Department of Pediatrics, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.

Abstract

Objective: To evaluate the association of enterovirus 71 (EV71) susceptibility and clinical severity with polymorphisms in EV71 receptors, including human scavenger receptor class B member 2 (SCARB2), P-selectin glycoprotein ligand-1 (PSGL-1), and annexin II (ANXA2).

Methods: We enrolled laboratory-confirmed EV71 cases and healthy age- and gender-matched controls in Taiwan from 2000 to 2012. We detected genetic polymorphisms in SCARB2, PSGL-1, and ANXA2 and correlated the results with EV71 susceptibility and severity.

Results: We collected 599 EV71 cases and 98 controls. Among EV71 patients, the male to female ratio was 1.61, and the mean age was 2.99±2.47 years. For clinical severity, 117 (19.6%) had severe central nervous system involvement with or without cardiopulmonary failure. For outcomes, 46 (7.7%) had sequelae, and 14 (2.3%) died. SCARB2 polymorphisms (rs6824953 and rs11097262) were associated with susceptibility to EV71 infection (OR 1.60, 95% CI 1.07-2.39; and OR 1.64, 95% CI 1.09-2.47, respectively). PSGL-1 polymorphisms (rs7137098 and rs8179137) were significantly associated with severe EV71 infection (OR 1.46, 95% CI 1.1-1.96; and OR 1.47, 95% CI 1.07-2.03, respectively).

Conclusions: SCARB2 polymorphisms (rs6824953 and rs11097262) might be associated with EV71 susceptibility. PSGL-1 polymorphisms (rs7137098 and rs8179137) were associated with severe EV71 infection.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Annexin A2 / genetics*
Case-Control Studies
Child, Preschool
Enterovirus A, Human / pathogenicity*
Enterovirus Infections / genetics*
Enterovirus Infections / virology
Female
Genetic Predisposition to Disease
Humans
Infant
Lysosomal Membrane Proteins / genetics*
Male
Membrane Glycoproteins / genetics*
Polymorphism, Single Nucleotide*
Receptors, Scavenger / genetics*
Receptors, Virus / genetics*
Severity of Illness Index
Taiwan

Substances

ANXA2 protein, human
Annexin A2
Lysosomal Membrane Proteins
Membrane Glycoproteins
P-selectin ligand protein
Receptors, Scavenger
Receptors, Virus
SCARB2 protein, human

Grants and funding

This study was supported by National Science Council grants, NSC 99-2321-B-002-025, NSC 100-2321-B-002-012, and NSC 101-2321-B-002-004 to Dr. Luan-Yin Chang, and China Medical University Hospital (DMR-100-188) to Dr. Ting-Yu Yen. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.