<i>IL‐4</i> gene polymorphisms and their relation to steroid‐induced osteonecrosis of the femoral head in Chinese population

Jin, Tianbo; Zhang, Yiming; Sun, Yao; Wu, Jia‐Min; Xiong, Zichao; Yang, Zhi

doi:10.1002/mgg3.563

Cited by 12 publications

(4 citation statements)

References 30 publications

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“…56 However, the SNP g.8455A>G rs2243289 of the IL-4 gene was associated with decreased risk of developing steroid-induced osteonecrosis of femoral head in Chinese population. 57 In current study, this SNP g.8455A>G was found in two confirmed positive patients of GI nematode infection who had severe signs and symptoms of disease, but association of this SNP in causing susceptibility to nematode infections cannot be done yet as more comprehensive case control study with large number of case and control samples should be conducted to confirm its association with nematode infections.…”

Section: Discussionmentioning

confidence: 69%

IL-4 gene polymorphisms and their association with nematodes infection in Pakistani population

Afshan¹,

Sarfraz²,

Kayani³

et al. 2022

Afr H. Sci.

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Background: Interleukin-4 (IL-4) plays a central role in the humoral immune defense against nematode parasite infections, inducing IgE switch and regulation of worm expulsion from the intestines. The present study aimed to investigate the polymorphisms in IL-4 gene and their association with socio-demographic and environmental factors among patients with gastrointestinal complaints. Method: The screened population comprised 305 patients aged 3-50 years from Rawalpindi and Jhelum districts of Pakistan. A well-prepared questionnaire was administered to collect data on socio-demographic and environmental factors. The data were analyzed by using multiple logistic regression models. Molecular analysis was done on 88 confirmed cases passing worms and eggs in stool by using PCR to amplify IL-4 gene. Results: The result showed higher GI nematodes prevalence in Rawalpindi 34.87% and Jhelum 23.1% among gastrointestinal patients. The multivariate logistic regression model showed significantly (p<0.05) increased risk of infection in participants who were residing in rural areas (OR=321.94; 22.5), having poor economic status (OR=0.34), consuming raw/unwashed vegetables (OR=1.73; 15.39) and did not practice handwashing (OR=2.77; OR=0.30). Sequence analysis showed three novel polymorphisms at SNP g.704_705 ins T, g.3763_3764 ins AC and g.3792 G >A in patients with acute severe infections. Two known polymorphisms SNPs g.8455A>G and g.8492C>A were found in the intron region. Conclusion: IL-4 gene polymorphisms showed disease susceptibility and consuming raw/unwashed vegetables, poor handwashing practices and poor economic status were the most associated factors with the disease. Keywords: Interleukin-4; SNPs; Nematodes; Risk Factors; Pakistan.

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Section: Discussionmentioning

confidence: 69%

IL-4 gene polymorphisms and their association with nematodes infection in Pakistani population

Afshan¹,

Sarfraz²,

Kayani³

et al. 2022

Afr H. Sci.

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“…We also found a correlation between IL-4 /GTT haplotype composed of rs2243283, rs2243250, rs2243248 and lower AD risk. As reported, rs2243283 gene variants have been confirmed to correlate to some chronic inflammatory and immune diseases, such as asthma, chronic periodontitis, and autoimmune hepatitis ( 22 ). However, as we know, rare studies focused on the linkage of this SNP with AD.…”

Section: Discussionmentioning

confidence: 82%

Association of IL-4 and IL-18 genetic polymorphisms with atopic dermatitis in Chinese children

Shi

Zheng

et al. 2023

Front. Pediatr.

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BackgroundAtopic dermatitis (AD) is a common chronic inflammatory skin disease, adversely affecting nearly 20% of the pediatric population worldwide. Interleukin-4 (IL-4) and interleukin-18 (IL-18) are considered to be involved in the pathogenesis and development of AD. The aim of this study was to investigate the association of IL-4 and IL-18 gene polymorphisms with the susceptibility and severity of AD in Chinese children.MethodsSix candidate single nucleotide polymorphisms (SNPs) in IL-4 and IL-18 genes were genotyped through multi-PCR combined with next-generation sequencing in 132 AD children and 100 healthy controls, and all the analyses were performed on blood genome DNA.ResultsThe frequencies of G allele, CG genotype and CG + GG genotype of IL-4 rs2243283, as well as the haplotype IL-4/GTT (rs2243283-rs2243250-rs2243248) were all significantly decreased in AD patients compared with the controls [G vs. C: P = 0.033, OR = 0.59; CG vs. CC: P = 0.024, OR = 0.47; CG + GG vs. CC: P = 0.012, OR = 0.49; GTT vs. CCT: P = 0.011, OR = 0.65]. Moreover, the frequencies of A allele, AA genotype and AG + AA genotype of IL-18 rs7106524, along with the haplotype IL-18/CAA (rs187238-rs360718-rs7106524) were statistically increased in the severe AD patients (A vs. G: P < 0.001, OR = 2.79; AA vs. GG: P = 0.003, OR = 5.51; AG + AA vs. GG: P = 0.036, OR = 2.93; CAA vs. CAG: P = 0.001, OR = 2.86).ConclusionsOur findings suggested that genetic variation in IL-4 rs2243283 such as G allele, CG genotype and CG + GG genotype might confer the reduced susceptibility to AD in Chinese children. Furthermore, A allele, AA genotype and AG + AA genotype of IL-18 rs7106524 explored the strong association with severity in Chinese AD children.

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“…Bradley and his colleagues’ studies showed that the inflammatory infiltrate in SONFH patients comprised primarily CD4(+) T cells and CD68(+) macrophages, the latter of which expressed increased levels of cellular adhesion molecules [ 40 ]. Tianbo et al suggested that polymorphisms of Interleukin-4 (IL-4) gene might be associated with susceptibility to SONFH, which helped reduce the infiltration of M1 phenotypic macrophages and maintain the activation of M2 phenotypic macrophages [ 41 ]. Mayu et al found that neutrophil extracellular traps-forming neutrophils were present in small vessels surrounding the femoral head of patients with ONFH but not osteoarthritis [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

IRF8 and its related molecules as potential diagnostic biomarkers or therapeutic candidates and immune cell infiltration characteristics in steroid-induced osteonecrosis of the femoral head

Liang

Liu

et al. 2023

J Orthop Surg Res

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Purpose Steroid-induced osteonecrosis of the femoral head (SONFH) was a refractory orthopedic hip joint disease in the young and middle-aged people, but the pathogenesis of SONFH remained unclear. We aimed to identify the potential genes and screen potential therapeutic compounds for SONFH. Methods The microarray was obtained for blood tissue from the GEO database, and then it identifies differentially expressed genes (DEGs). The DEGs were analyzed to obtain the differences in immune cell infiltration. The gene functional enrichment analysis of SONFH was analyzed. The PPI of DEGs was identified through the STRING database, and the cluster modules and hub genes were ascertained using MCODE and CytoHubba, and the ROC curve of hub genes was analyzed, and the tissues distribution of hub genes was understood by the HPA, Bgee and BioGPS databases. The hub genes and target miRNAs and corresponding upstream lncRNAs were predicted by TargetScan, miRDB and ENCORI database. Subsequently, we used CMap, DGIdb and L1000FWD databases to identify several potential therapeutic molecular compounds for SONFH. Finally, the AutoDockTools Vina, PyMOL and Discovery Studio were employed for molecular docking analyses between compounds and hub genes. Results The microarray dataset GSE123568 was obtained related to SONFH. There were 372 DEGs including 197 upregulated genes and 175 downregulated genes by adjusted P value < 0.01 and |log2FC|> 1. Several significant GSEA enrichment analysis and biological processes and KEGG pathway associated with SONFH were identified, which were significantly related to cytoskeleton organization, nucleobase-containing compound catabolic process, NOD-like receptor signaling pathway, MAPK signaling pathway, FoxO signaling pathway, neutrophil-mediated immunity, neutrophil degranulation and neutrophil activation involved in immune response. Activated T cells CD4 memory, B cells naïve, B cells memory, T cells CD8 and T cells gamma delta might be involved in the occurrence and development of SONFH. Three cluster modules were identified in the PPI network, and eleven hub genes including FPR2, LILRB2, MNDA, CCR1, IRF8, TYROBP, TLR1, HCK, TLR8, TLR2 and CCR2 were identified by Cytohubba, which were differed in bone marrow, adipose tissue and blood, and which had good diagnostic performance in SONFH. We identified IRF8 and 10 target miRNAs that was utilized including Targetsan, miRDB and ENCORI databases and 8 corresponding upstream lncRNAs that was revealed by ENCORI database. IRF8 was detected with consistent expression by qRT-PCR. Based on the CMap, DGIdb and L1000FWD databases, the 11 small molecular compounds that were most strongly therapeutic correlated with SONFH were estradiol, genistein, domperidone, lovastatin, myricetin, fenbufen, rosiglitazone, sirolimus, phenformin, vorinostat and vinblastine. All of 11 small molecules had good binding affinity with the IRF8 in molecular docking. Conclusion The occurrence of SONFH was associated with a “multi-target” and “multi-pathway” pattern, especially related to immunity, and IRF8 and its noncoding RNA were closely related to the development of SONFH. The CMap, DGIdb and L1000FWD databases could be effectively used in a systematic manner to predict potential drugs for the prevention and treatment of SONFH. However, additional clinical and experimental research is warranted.

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IL‐4 gene polymorphisms and their relation to steroid‐induced osteonecrosis of the femoral head in Chinese population

Cited by 12 publications

References 30 publications

IL-4 gene polymorphisms and their association with nematodes infection in Pakistani population

IL-4 gene polymorphisms and their association with nematodes infection in Pakistani population

Association of IL-4 and IL-18 genetic polymorphisms with atopic dermatitis in Chinese children

IRF8 and its related molecules as potential diagnostic biomarkers or therapeutic candidates and immune cell infiltration characteristics in steroid-induced osteonecrosis of the femoral head

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