DNA methylation and single-nucleotide polymorphisms in DDX58 are associated with hand, foot and mouth disease caused by enterovirus 71.
<h4>Background</h4>This research aimed to explore the association between the RIG-I-like receptor (RIG-I and MDA5 encoded by DDX58 and IFIH1, respectively) pathways and the risk or severity of hand, foot, and mouth disease caused by enterovirus 71 (EV71-HFMD). In this context, we explore...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2022-01-01
|
| Series: | PLoS Neglected Tropical Diseases |
| Online Access: | https://doi.org/10.1371/journal.pntd.0010090 |
| _version_ | 1818975005815341056 |
|---|---|
| author | Ya-Ping Li Chen-Rui Liu Hui-Ling Deng Mu-Qi Wang Yan Tian Yuan Chen Yu-Feng Zhang Shuang-Suo Dang Song Zhai |
| author_facet | Ya-Ping Li Chen-Rui Liu Hui-Ling Deng Mu-Qi Wang Yan Tian Yuan Chen Yu-Feng Zhang Shuang-Suo Dang Song Zhai |
| author_sort | Ya-Ping Li |
| collection | DOAJ |
| description | <h4>Background</h4>This research aimed to explore the association between the RIG-I-like receptor (RIG-I and MDA5 encoded by DDX58 and IFIH1, respectively) pathways and the risk or severity of hand, foot, and mouth disease caused by enterovirus 71 (EV71-HFMD). In this context, we explored the influence of gene methylation and polymorphism on EV71-HFMD.<h4>Methodology/principal findings</h4>60 healthy controls and 120 EV71-HFMD patients, including 60 mild EV71-HFMD and 60 severe EV71-HFMD patients, were enrolled. First, MiSeq was performed to explore the methylation of CpG islands in the DDX58 and IFIH1 promoter regions. Then, DDX58 and IFIH1 expression were detected in PBMCs using RT-qPCR. Finally, imLDR was used to detect DDX58 and IFIH1 single-nucleotide polymorphism (SNP) genotypes. Severe EV71-HFMD patients exhibited higher DDX58 promoter methylation levels than healthy controls and mild EV71-HFMD patients. DDX58 promoter methylation was significantly associated with severe HFMD, sex, vomiting, high fever, neutrophil abundance, and lymphocyte abundance. DDX58 expression levels were significantly lower in mild patients than in healthy controls and lower in severe patients than in mild patients. Binary logistic regression analysis revealed statistically significant differences in the genotype frequencies of DDX58 rs3739674 between the mild and severe groups. GeneMANIA revealed that 19 proteins displayed correlations with DDX58, including DHX58, HERC5, MAVS, RAI14, WRNIP1 and ISG15, and 19 proteins displayed correlations with IFIH1, including TKFC, IDE, MAVS, DHX58, NLRC5, TSPAN6, USP3 and DDX58.<h4>Conclusions/significance</h4>DDX58 expression and promoter methylation were associated with EV71 infection progression, especially in severe EV71-HFMD patients. The effect of DDX58 in EV71-HFMD is worth further attention. |
| first_indexed | 2024-12-20T15:49:05Z |
| format | Article |
| id | doaj.art-c7f37fc07d0147399952e111ba49029d |
| institution | Directory Open Access Journal |
| issn | 1935-2727 1935-2735 |
| language | English |
| last_indexed | 2024-12-20T15:49:05Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Neglected Tropical Diseases |
| spelling | doaj.art-c7f37fc07d0147399952e111ba49029d2022-12-21T19:34:46ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352022-01-01161e001009010.1371/journal.pntd.0010090DNA methylation and single-nucleotide polymorphisms in DDX58 are associated with hand, foot and mouth disease caused by enterovirus 71.Ya-Ping LiChen-Rui LiuHui-Ling DengMu-Qi WangYan TianYuan ChenYu-Feng ZhangShuang-Suo DangSong Zhai<h4>Background</h4>This research aimed to explore the association between the RIG-I-like receptor (RIG-I and MDA5 encoded by DDX58 and IFIH1, respectively) pathways and the risk or severity of hand, foot, and mouth disease caused by enterovirus 71 (EV71-HFMD). In this context, we explored the influence of gene methylation and polymorphism on EV71-HFMD.<h4>Methodology/principal findings</h4>60 healthy controls and 120 EV71-HFMD patients, including 60 mild EV71-HFMD and 60 severe EV71-HFMD patients, were enrolled. First, MiSeq was performed to explore the methylation of CpG islands in the DDX58 and IFIH1 promoter regions. Then, DDX58 and IFIH1 expression were detected in PBMCs using RT-qPCR. Finally, imLDR was used to detect DDX58 and IFIH1 single-nucleotide polymorphism (SNP) genotypes. Severe EV71-HFMD patients exhibited higher DDX58 promoter methylation levels than healthy controls and mild EV71-HFMD patients. DDX58 promoter methylation was significantly associated with severe HFMD, sex, vomiting, high fever, neutrophil abundance, and lymphocyte abundance. DDX58 expression levels were significantly lower in mild patients than in healthy controls and lower in severe patients than in mild patients. Binary logistic regression analysis revealed statistically significant differences in the genotype frequencies of DDX58 rs3739674 between the mild and severe groups. GeneMANIA revealed that 19 proteins displayed correlations with DDX58, including DHX58, HERC5, MAVS, RAI14, WRNIP1 and ISG15, and 19 proteins displayed correlations with IFIH1, including TKFC, IDE, MAVS, DHX58, NLRC5, TSPAN6, USP3 and DDX58.<h4>Conclusions/significance</h4>DDX58 expression and promoter methylation were associated with EV71 infection progression, especially in severe EV71-HFMD patients. The effect of DDX58 in EV71-HFMD is worth further attention.https://doi.org/10.1371/journal.pntd.0010090 |
| spellingShingle | Ya-Ping Li Chen-Rui Liu Hui-Ling Deng Mu-Qi Wang Yan Tian Yuan Chen Yu-Feng Zhang Shuang-Suo Dang Song Zhai DNA methylation and single-nucleotide polymorphisms in DDX58 are associated with hand, foot and mouth disease caused by enterovirus 71. PLoS Neglected Tropical Diseases |
| title | DNA methylation and single-nucleotide polymorphisms in DDX58 are associated with hand, foot and mouth disease caused by enterovirus 71. |
| title_full | DNA methylation and single-nucleotide polymorphisms in DDX58 are associated with hand, foot and mouth disease caused by enterovirus 71. |
| title_fullStr | DNA methylation and single-nucleotide polymorphisms in DDX58 are associated with hand, foot and mouth disease caused by enterovirus 71. |
| title_full_unstemmed | DNA methylation and single-nucleotide polymorphisms in DDX58 are associated with hand, foot and mouth disease caused by enterovirus 71. |
| title_short | DNA methylation and single-nucleotide polymorphisms in DDX58 are associated with hand, foot and mouth disease caused by enterovirus 71. |
| title_sort | dna methylation and single nucleotide polymorphisms in ddx58 are associated with hand foot and mouth disease caused by enterovirus 71 |
| url | https://doi.org/10.1371/journal.pntd.0010090 |
| work_keys_str_mv | AT yapingli dnamethylationandsinglenucleotidepolymorphismsinddx58areassociatedwithhandfootandmouthdiseasecausedbyenterovirus71 AT chenruiliu dnamethylationandsinglenucleotidepolymorphismsinddx58areassociatedwithhandfootandmouthdiseasecausedbyenterovirus71 AT huilingdeng dnamethylationandsinglenucleotidepolymorphismsinddx58areassociatedwithhandfootandmouthdiseasecausedbyenterovirus71 AT muqiwang dnamethylationandsinglenucleotidepolymorphismsinddx58areassociatedwithhandfootandmouthdiseasecausedbyenterovirus71 AT yantian dnamethylationandsinglenucleotidepolymorphismsinddx58areassociatedwithhandfootandmouthdiseasecausedbyenterovirus71 AT yuanchen dnamethylationandsinglenucleotidepolymorphismsinddx58areassociatedwithhandfootandmouthdiseasecausedbyenterovirus71 AT yufengzhang dnamethylationandsinglenucleotidepolymorphismsinddx58areassociatedwithhandfootandmouthdiseasecausedbyenterovirus71 AT shuangsuodang dnamethylationandsinglenucleotidepolymorphismsinddx58areassociatedwithhandfootandmouthdiseasecausedbyenterovirus71 AT songzhai dnamethylationandsinglenucleotidepolymorphismsinddx58areassociatedwithhandfootandmouthdiseasecausedbyenterovirus71 |