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Association of functional polymorphisms in the MxA gene with susceptibility to enterovirus 71 infection

Xiaoai Zhang1, Hongmei Xu, Xiaodan Chen

  • 1State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, 20 Dong-Da Street Fengtai District, Beijing, 100071, People's Republic of China.

Human Genetics
|October 3, 2013
PubMed

Insights

Myxovirus resistance A (MxA) gene variations may reduce the risk of enterovirus 71 (EV71) infection. MxA promoter polymorphisms are linked to lower EV71 susceptibility and higher MxA protein levels in Chinese populations.

Area of Science:

  • Genetics
  • Immunology
  • Virology

Background:

  • Myxovirus resistance A (MxA) is an interferon-induced antiviral protein crucial for inhibiting viral replication.
  • Enterovirus 71 (EV71) causes significant human disease, particularly in children.
  • Genetic variations in antiviral proteins like MxA could influence susceptibility to viral infections.

Purpose of the Study:

  • To investigate the association between MxA gene polymorphisms and the risk and severity of EV71 infection in Chinese populations.
  • To determine if MxA promoter variations impact MxA protein expression levels in response to interferon stimulation.

Main Methods:

  • Genotyping of MxA C-123A and G-88T polymorphisms using PCR-RFLP in two independent Chinese case-control populations.
  • Multivariate logistic regression analysis to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs).
  • Quantification of MxA mRNA levels in peripheral blood mononuclear cells (PBMCs) via real-time quantitative PCR.

Main Results:

  • Both the -123A and -88T MxA alleles were significantly associated with decreased susceptibility to EV71 infection in both northern and southern Chinese populations (ORs ranging from 0.56 to 0.67).
  • The A-123T-88 MxA haplotype also showed a significant association with reduced EV71 infection risk (ORs around 0.62-0.63).
  • Individuals carrying the -123A or -88T alleles exhibited higher MxA mRNA levels upon IFNβ1a stimulation compared to non-carriers.

Conclusions:

  • Polymorphisms in the MxA promoter region are associated with differential susceptibility to EV71 infection in the Chinese population.
  • These MxA genetic variations may influence the host's innate immune response to EV71.
  • The findings highlight the potential role of MxA genetic background in modulating EV71 pathogenesis.

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