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

Abstract

Myxovirus resistance A (MxA) is an antiviral protein induced by type I interferons α and β (IFN-α and IFN-β) that can inhibit virus replication. We examined whether the MxA polymorphisms were related to the risk and severity of enterovirus 71 (EV71) infection in Chinese populations. The MxA C-123A and G-88T polymorphisms were genotyped in two independent case-control populations in China by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) analysis. Multivariate logistic regression analysis was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). MxA messenger RNA was quantified by real-time quantitative PCR in peripheral blood mononuclear cells (PBMCs) from 45 healthy children and 19 patients with EV71 infection. Significantly decreased susceptibility to EV71 infection was observed for the -123A allele and -88T allele carriers, with ORs (95% CIs) estimated as 0.56 (0.39-0.81) and 0.64 (0.47-0.88), respectively, in the northern population. This association was confirmed in the southern population, with ORs (95% CIs) estimated as 0.58 (0.38-0.89) and 0.67(0.47-0.95), respectively. The A- 123T- 88 haplotype was also significantly associated with lower risk of EV71 infection in both the northern (OR = 0.62; 95% CI = 0.44-0.85) and the southern population (OR = 0.63; 95% CI = 0.43-0.92). Furthermore, we observed higher MxA messenger RNA levels in IFNβ1a-stimulated PBMCs from the -123A or -88T allele carriers compared with that from nocarriers. Our findings suggest that polymorphisms in the MxA promoter may play a role in mediating the susceptibility to EV71 infection in Chinese population.

Mx genes: host determinants controlling influenza virus infection and trans-species transmission

“…Much previous work has also been focused on noncoding regions of MX1. Variations in the promoter region − 123(C/A) and − 88(G7T) affecting MxA expression levels seem to influence disease outcomes of patients with hepatitis B and C as well as SARS and enterovirus 71 (Cao et al 2009;Ching et al 2010;Hamano et al 2005;He et al 2006;Hijikata et al 2000;Knapp et al 2003;Kong et al 2007;Suzuki et al 2004;Zhang et al 2014). Furthermore, an SNP in intron 3 was linked to increased risk for symptomatic West Nile virus infection (Bigham et al 2011).…”

A functional polymorphism in IFNAR1 gene is associated with susceptibility and severity of HFMD with EV71 infection

“…All together prompt that host genetic background plays an important role in the occurrence and development of EV71 HFMD. Polymorphisms of type I IFN signaling pathway genes like MX1 and OAS1 have been reported to link to the occurrence and development of HFMD 18 19 . Other variants of type II IFN related genes IFN-γ, IL-10 and IP-10, chemokines CCL2 and CXCL10 and eNOS also contributed to susceptibility or severity to EV71 infection 20 21 22 23 .…”

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

“…Association of EV71 infection with cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), human leukocyte antigen (HLA)-A33, IL-10, IFN-γ, MxA, and eNOS gene polymorphisms has already been reported. [16][17][18][19][20] In this study, we explored the possible correlation of the polymorphisms of -403G/A (rs2107538), -28C/G (rs2280788), and In1.1T/C (rs2280789) in the CCL5 gene with the severe EV71 infection. We hope that our results provide insights into protective and pathogenic mechanisms in EV71 infection.…”