Association of the IRAK4 rs4251545 genetic polymorphism with severity of enterovirus‐71 infection in Chinese children

Abstract

Introduction: This study aimed to explore the association between the IRAK4 polymorphism rs4251545 and the severity of enterovirus 71 (EV71) infection in Chinese children. Methods: We analyzed the IRAK4 polymorphism rs4251545 in 617 EV71infected patients and 410 controls using the improved multiplex ligation detection reaction. IRAK4 mRNA expression was tested by qRT-PCR. Serum concentrations of IL-6 and NF-κB were detected using ELISA. Results:The frequencies of the GA + AA genotype and A allele in the mild EV71 infection group and in the severe EV71 infection group were significantly higher than those in the normal control group. The frequency of the GA + AA genotype and A allele in severely infected EV71 patients was markedly higher than that in mildly infected EV71 patients. IRAK4 mRNA expression in mildly infected EV71 patients and severely infected patients was significantly higher than that in the control group. IRAK4 mRNA expression in GA + AA genotypes in both mild and severe EV71 infection groups was significantly higher than that in patients with the GG genotype. IL-6 concentration and the ratio of IL-6/NF-κB in severe EV71 cases were significantly lower in patients with the GA + AA genotype than in those with the GG genotype. The ratio of IL-6/NF-κB was distinctly higher in severely infected EV71 patients than in mildly infected and control subjects. Conclusions: The IRAK4 polymorphism rs4251545 was associated with the susceptibility and severity of EV71 infection. The A allele is a susceptible factor in the development of severe EV71 infection in Chinese children.

TMEM173 rs7447927 genetic polymorphism and susceptibility to severe enterovirus 71 infection in Chinese children

“… 2 Therefore, exploring the pathogenic mechanism of severe infections and effectively preventing their occurrence are still priorities for current research. Previous studies by Chen et al have shown that SNP in multiple host inflammation‐related genes, such as TLR3 , IL‐8 , CPT2 , and IRAK4 , 6 , 7 , 13 , 14 are associated with susceptibility to severe EV71 infection. It has been speculated that TMEM173 , as an interferon stimulating factor and cGAMP interacting factor, may be involved in the immune, inflammatory, and cell death processes triggered by viral infections.…”

Two novel compound heterozygous loss-of-function mutations cause fetal IRAK-4 deficiency presenting with Pseudomonas Aeruginosa sepsis

“…As an autosomal recessive disorder, IRAK-4 de ciency patients always have homozygous or compound heterozygous mutations in IRAK4 [5,28]. The human IRAK4 gene, located on chromosome 12q12, includes 11 exons and 10 introns, and encodes 460 amino acid protein [29]. In this study, two novel compound heterozygous mutations in IRAK4 were identi ed using the Trio-WES approach in this patient, and the functional consequences of these mutations were con rmed to be loss-of-expression by in vitro minigene splicing assays.…”

Unraveling Extremely Damaging IRAK4 Variants and Their Potential Implications for IRAK4 Inhibitor Efficacy

“…In addition, it has been established that IRAK4 deficiency is correlated with the compromise of toll-like receptor (TLR)/IL-1R-mediated immunity, resulting in heightened vulnerability to recurring bacterial infections that pose a significant risk to one's life [32]. Furthermore, it has been observed that certain single-nucleotide polymorphisms (SNPs) in the IRAK4 gene are correlated with various infectious and malignant diseases [2,[23][24][25][26]. As a result, the identification of the most harmful missense single-nucleotide polymorphisms (SNPs) in the IRAK4 gene has become imperative in the investigation process of this significant biomolecule.…”

“…This has accompanied the recent remarkable usage of computational methods in initial studies in many biological fields [21,22]. Research has indicated that the presence of IRAK4 genetic variants is associated with various infectious diseases, including severe sepsis, heightened occurrence of Gram-positive infection, and increased severity and vulnerability of enterovirus 71 infection [2,23,24]. Furthermore, there is evidence suggesting a correlation between genetic variations in IRAK4 and the occurrence of certain types of cancer, such as breast cancer, as well as the advancement of hepatocellular carcinoma (HCC) related to hepatitis B virus (HBV) [25,26].…”