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Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Association analysis of polymorphisms in OAS1 with susceptibility and severity of hand, foot and mouth disease
Insights
Genetic variations in children can help identify Hand, Foot, and Mouth Disease (HFMD) susceptibility. The OAS1 rs10774671 GG genotype is linked to increased risk of coxsackievirus A16 infection and milder disease progression.
Area of Science:
- Genetics
- Virology
- Immunology
Background:
- Hand, Foot, and Mouth Disease (HFMD) is a prevalent childhood illness, primarily affecting children under five in Asia.
- Human Enterovirus 71 (EV71) and Coxsackievirus A16 (CA16) are the main causative agents of HFMD.
- Early screening and identification of severe cases through genetic variation detection are crucial for managing HFMD.
Purpose of the Study:
- To investigate the association between specific single-nucleotide polymorphisms (SNPs) and susceptibility to HFMD.
- To determine if genetic variations can predict disease severity and progression in children.
- To explore the relationship between genetic factors, viral load, and immune responses in HFMD patients.
Main Methods:
- Taqman assays were employed to genotype four SNPs (OAS1 rs10774671, SELPLG rs2228315, SCARB2 rs41284767, IL28B rs12979860) in 333 HFMD patients and 163 controls.
- Enzyme-linked immunosorbent assay (ELISA) was used to measure plasma gamma-interferon (IFN) levels.
- Linear correlation analysis was performed to assess the relationship between IFN levels and OAS1 rs10774671 genotypes.
Main Results:
- The OAS1 rs10774671 polymorphism showed a significant difference between controls and CA16-infected children, with the GG genotype associated with higher susceptibility.
- The rs10774671 genotype distribution differed significantly between severe and mild HFMD cases, with AA+AG genotypes linked to a higher likelihood of encephalitis.
- Mild HFMD cases exhibited higher gamma-IFN levels than severe cases, and the OAS1 rs10774671 GG genotype correlated with elevated gamma-IFN levels.
Conclusions:
- The OAS1 rs10774671 SNP GG genotype is a potential genetic marker for increased susceptibility to CA16-type HFMD.
- This genotype is associated with a milder form of HFMD and potentially reduced risk of severe complications like encephalitis.
- Gamma-interferon levels are linked to both OAS1 rs10774671 genotype and HFMD severity, suggesting a role in the host immune response.
Abstract:
Hand, foot and mouth disease (HFMD) is a common childhood illness that mainly affects Asian children under the age of 5 years. Human enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are the most common pathogens of HFMD. It is imperative that the susceptible population is screened early and that the severe illness population can be identified via genetic variation detection in children. Four single-nucleotide polymorphisms (SNP) [2'-5'-oligoadenylate synthetase1 (OAS1) rs10774671, selectin P ligand (SELPLG) rs2228315, scavenger receptor class B member 2 (SCARB2) rs41284767 and interleukin 28B (IL28B) rs12979860] were determined by Taqman assays in 333 HFMD samples and 163 control samples. The rs2228315, rs41284767 and rs12979860 polymorphisms did not differ significantly between HFMD patients and the controls, but the prevalence of the rs10774671 polymorphism was significantly different between the control children and children infected with CA16 (GG genotype vs. AA + AG genotype, P < 0.05). Children with the GG genotype were more susceptible to CA16-type HFMD. Furthermore, the rs10774671 genotype distribution was clearly different between children with severe HFMD and those with mild HFMD [P < 0.05, OR 0.240, 95% CI (0.071-0.809)]. HFMD children with the AA+AG genotype were more likely to progress to encephalitis than were those with the GG genotype. Plasma γ-interferon (IFN) expression levels among control children and the mild and severe HFMD children were detected by ELISA. Those with mild HFMD had higher γ-IFN expression levels compared with those with severe HFMD (P < 0.05). In addition, there is a significant correlation between γ-IFN levels and OAS1 rs10774671 SNP, as analysed by linear correlation assay. The GG genotype correlated with higher γ-IFN levels (P < 0.05). In short, the OAS1 rs10774671 SNP GG genotype contributed to CA16 susceptibility and was associated with the development of mild HFMD.
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