Key result
Lower IFITM3 promoter methylation and the rs12252 G allele were associated with severe EV71-HFMD progression compared to mild cases and healthy controls.
Why the study?
The study was conducted to explore the mechanisms of IFITM3 in response to EV71-HFMD regarding DNA methylation, SNP genotype, and gene expression.
Do IFITM3 methylation status and SNP genotype correlate with the severity of EV71-associated hand, foot and mouth disease?
Case-Control (n=180)
Do IFITM3 methylation status and SNP genotype correlate with the severity of EV71-associated hand, foot and mouth disease?
IFITM3 promoter hypomethylation and the rs12252 GG genotype are associated with increased severity of EV71-associated hand, foot and mouth disease.
Lower IFITM3 methylation and rs12252-G associate with severe EV71-HFMD; hypothesis-generating for methylation/SNP-based stratification pending prospective validation.
OBJECTIVES: To explore the mechanisms of interferon-induced transmembrane protein 3 (IFITM3) in response to enterovirus-71-associated hand, foot and mouth disease (EV71-HFMD), in terms of DNA methylation, single-nucleotide polymorphism (SNP) genotype and gene expression. METHODS: In total, 120 patients with EV71-HFMD (60 with mild EV71-HFMD and 60 with severe EV71-HFMD) and 60 healthy controls were enrolled in this study. SNP genotype, IFITM3 promoter methylation and mRNA expression of peripheral blood mononuclear cells were examined using the improved multi-temperature ligase detection reaction, quantitative reverse transcriptase polymerase chain reaction and MiSeq, respectively. RESULTS: The distribution of methylation in patients with EV71-HFMD was significantly lower compared with healthy controls, and the severe EV71-HFMD group showed the lowest frequency of IFITM3 promoter methylation. The average level of IFITM3 promoter CpG methylation was negatively correlated with IFITM3 mRNA expression, and hypermethylation of several specific CpG units contributed to IFITM3 downregulation. IFITM3 expression and promoter methylation correlated with EV71 infection progression, especially in the severe EV71-HFMD group. Compared with mild cases, genotype GG and the G allele of rs12252 were over-represented in patients with severe EV71-HFMD. CONCLUSIONS: IFITM3 methylation status and SNP genotyping may help clinicians to choose the correct treatment strategy for patients with EV71-HFMD.
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Li et al. (2021) conducted a case-control in enterovirus-71-associated hand, foot and mouth disease (EV71-HFMD) (n=180). IFITM3 promoter methylation and SNP genotype vs. Healthy controls and mild EV71-HFMD cases was evaluated on IFITM3 promoter methylation and mRNA expression. Lower IFITM3 promoter methylation and the rs12252 G allele were associated with severe EV71-HFMD progression compared to mild cases and healthy controls.
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