腸病毒整合性生物資訊計畫-功能基因體學,宿主易感基因之研究與應用─腸病毒71型宿主基因分析-找尋易感染或抗感染之基因（子計畫五）
Date Issued
2003
Date
2003
Author(s)
張鑾英
DOI
913112B002029
Abstract
EV71 has caused large epidemics with lots of fatal cases and cases with sequelae.
However, the clinical syndromes and severity of the same EV71 strain are very diverse,
ranging from asymptomatic (71%) to fatal (0.05%) diseases. To date, no clear viral virulence
factor has been found and there is no association between EV71 genotypes and clinical
outcomes. Therefore, host factors may be important to the clinical outcomes of EV71
infections. By investigating host genetic background, we may find some genetic variants that
influence susceptibility and disease severity to EV71 infection.
A total of 150 EV71 cases were collected and about 100 control cases had been
collected. The clinical diagnosis and outcome of the 150 EV71 cases are as the following:
38% (57/150) of the cases were uncomplicated, 44% (66/150) of our EV71 cases had central
nervous system involvement, such as meningitis, myoclonic jerk, encephalitis, polio-like
syndrome, etc and 18% (27/150) developed cardiopulmonary failure soon after CNS
involvement. After intensive resuscitation and medical care, eleven (7%) children died and
36 (24%) children had sequelae of dysphagia, central hypoventilation, cranial nerve palsy
and limb weakness/atrophy.
With PCR, SNP detection with appropriate restriction enzyme and automatic gene
sequencing, polymorphisms of immune-related genes are being studied and correlated with
susceptibility and clinical outcomes of EV71 infection. In allelic association study for the
candidate genes with case-control study, EV71 cases had higher percentage of type II TNF-a
promoter polymorphism in comparison with normal control children (26% vs. 14%, p=0.045).
However, there was no significant difference of IL6 promoter polymorphism between EV71
cases and normal control children. TNF-a promoter polymorphism did not correlate with
clinical severity and clinical outcome. IL6 promoter polymorphism did not correlate with
clinical severity and clinical outcome, either. From our preliminary results, TNF-a promoter
polymorphism seem related to susceptibility of EV71 infection and whether the TNF-a
promoter regulates or enhances the susceptibility of EV71 needs further investigation.
Further case collection, and sequencing of other immune-related genes and the second
group of candidate genes such as EV71 receptor and their regulatory genes will be done in
the future. Thereafter, we will compare genetic variants among EV71 cases with different
severity and normal children to find susceptible or resistant genes and genetic polymorphism
related to clinical outcomes, to find the strength of disease associations with different
combinations of polymorphism.
Subjects
EV71
host factor
genetic var iants
clinical outcome
SDGs
Publisher
臺北市：國立臺灣大學醫學院小兒科
Type
report
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