IRAK2 is associated with systemic lupus erythematosus risk

Boumiza, Asma; Zemni, Ramzi; Sghiri, Rim; Idriss, Nadia; Hassine, Habib; Chabchoub, Elyes; Mzabi, A.; Ghannouchi, N.; Bouajina, E.; Slama, Foued

doi:10.1007/s10067-019-04781-1

Cited by 3 publications

(3 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of these, we found that IRAK2 showed the maximum fold change of gene expression ( Figure 1B ). Hence, we chose IRAK2 as our target for further functional analysis because it plays a vital role in regulating innate immunity ( 22 ) and may have great potential in predicting radiation response of OSCC cells. The data showed that the RPKM value of IRAK2 expression of the OML1-R was lower than that of OML1 cell lines whether control or IR treatment ( Figure 1C ).…”

Section: Resultsmentioning

confidence: 99%

IRAK2, an IL1R/TLR Immune Mediator, Enhances Radiosensitivity via Modulating Caspase 8/3-Mediated Apoptosis in Oral Squamous Cell Carcinoma

Chan

Lin

et al. 2021

Front. Oncol.

View full text Add to dashboard Cite

Predicting and overcoming radioresistance are crucial in radiation oncology, including in managing oral squamous cell carcinoma (OSCC). First, we used RNA-sequence to compare expression profiles of parent OML1 and radioresistant OML1-R OSCC cells in order to select candidate genes responsible for radiation sensitivity. We identified IRAK2, a key immune mediator of the IL-1R/TLR signaling, as a potential target in investigating radiosensitivity. In four OSCC cell lines, we observed that intrinsically low IRAK2 expression demonstrated a radioresistant phenotype (i.e., OML1-R and SCC4), and vice versa (i.e., OML1 and SCC25). Next, we overexpressed IRAK2 in low IRAK2-expression OSCC cells and knocked it down in high IRAK2-expression cells to examine changes of irradiation response. After ionizing radiation (IR) exposure, IRAK2 overexpression enhanced the radiosensitivity of radioresistant cells and synergistically suppressed OSCC cell growth both in vitro and in vivo, and vice versa. We found that IRAK2 overexpression restored and enhanced radiosensitivity by enhancing IR-induced cell killing via caspase-8/3-dependent apoptosis. OSCC patients with high IRAK2 expression had better post-irradiation local control than those with low expression (i.e., 87.4% vs. 60.0% at five years, P = 0.055), showing that IRAK2 expression was associated with post-radiation recurrence. Multivariate analysis confirmed high IRAK2 expression as an independent predictor for local control (HR, 0.11; 95% CI, 0.016 – 0.760; P = 0.025). In conclusion, IRAK2 enhances radiosensitivity, via modulating caspase 8/3-medicated apoptosis, potentially playing double roles as a predictive biomarker and a novel therapeutic target in OSCC.

show abstract

Section: Resultsmentioning

confidence: 99%

IRAK2, an IL1R/TLR Immune Mediator, Enhances Radiosensitivity via Modulating Caspase 8/3-Mediated Apoptosis in Oral Squamous Cell Carcinoma

Chan

Lin

et al. 2021

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…19 Two studies reported a significant association of SNP rs708035 with diseases including rheumatoid arthritis and systemic lupus erythematosus. 18,20 A study also reported involvement of SNP rs708035 in the regulation of NF-κB and the substitution of nucleotide A > T results in amino acid change (aspartate to glutamate) at position 431 (D431E), which is involved in the enhanced polyubiquitination of TRAF6 and increased transcription of NF-κB. 7 Reportedly, the current study for the first time evaluates the association of IRAK2 SNP rs708035 among the leprosy patients.…”

Section: Discussionmentioning

confidence: 71%

“…The risk association of the heterozygous genotype A/T of IRAK2 SNP ( rs708035 ) was also reported among the rheumatoid arthritis patients of the Pakistani population 19 . Two studies reported a significant association of SNP rs708035 with diseases including rheumatoid arthritis and systemic lupus erythematosus 18,20 . A study also reported involvement of SNP rs708035 in the regulation of NF‐ κ B and the substitution of nucleotide A > T results in amino acid change (aspartate to glutamate) at position 431 (D431E), which is involved in the enhanced polyubiquitination of TRAF6 and increased transcription of NF‐ κ B 7 …”

Section: Discussionmentioning

confidence: 86%

Hyperfunction variant rs708035 of interleukin 1 receptor‐associated kinases 2 gene involved in the predisposition of leprosy infection

Saleem

Zia²,

Siddiqui

et al. 2023

The Journal of Gene Medicine

View full text Add to dashboard Cite

Background Mycobacterium leprae (slow‐growing bacteria) is the etiological agent for leprosy infection, which is a chronic granulomatous disease. Symptoms initiate with the loss of sensation in the affected areas, which can lead to severe injuries, cuts and burns. IRAK2 (interleukin‐1 receptor‐associated kinases 2) is reported to function in the regulation of the NFκB pathway. The frequency of the IRAK2 polymorphism (rs708035) was unknown in the Pakistani population. Therefore, the study was designed to identify the role of the rs708035 SNP (single nucleotide polymorphism) in susceptibility to leprosy. Methodology The case–control study was designed, and participants were selected by Ridley–Jopling Classification. Blood samples from healthy individuals and patients were collected after ethical approval. Genomic DNA was extracted for the amplification of selected polymorphisms by tetra‐primer amplification refractory mutation system polymerase chain reaction. The desired products were observed via agarose gel (2.5%) electrophoresis followed by data analysis using bioinformatics tools (SNP Stats and SHEsis) and statistical tests (odds ratio, OR, and chi square). Results The study revealed that the mutant genotype (TT) was found to be frequent among cases (22.80%) in comparison with the controls (1.66%). The SNP rs708035 was significantly associated with the progression of leprosy (χ2 = 17.62, p < 0.0001). The targeted SNP significantly increases the risk of leprosy 2.3 times (OR = 2.3119, 95% CI 1.2729–4.1989, p < 0.01). The genetic model also confirms the significant association of the A/T genotype with leprosy in the over‐dominant model (OR = 2.83, 95% CI 1.16–6.89, p < 0.001). Conclusions The study revealed a significant association of the targeted SNP with leprosy and provided baseline data regarding the association of rs708035. The current research could be utilized for the preparation of biomarkers by considering a larger sample size. Highlights The patients suffering from leprosy faced various comorbidities, including hypertension and diabetes. The study reports for the first time a significant association of interleukin 1 receptor associated kinases 2 (IRAK2) single nucleotide polymorphism (SNP) rs708035 among the Pakistani population (Karachi). The current study provides baseline data to develop diagnostic biomarkers for early detection of leprosy.

show abstract

A CD40 variant is associated with systemic bone loss among patients with rheumatoid arthritis

et al. 2022

View full text Add to dashboard Cite

IRAK2 is associated with systemic lupus erythematosus risk

Cited by 3 publications

References 34 publications

IRAK2, an IL1R/TLR Immune Mediator, Enhances Radiosensitivity via Modulating Caspase 8/3-Mediated Apoptosis in Oral Squamous Cell Carcinoma

IRAK2, an IL1R/TLR Immune Mediator, Enhances Radiosensitivity via Modulating Caspase 8/3-Mediated Apoptosis in Oral Squamous Cell Carcinoma

Hyperfunction variant rs708035 of interleukin 1 receptor‐associated kinases 2 gene involved in the predisposition of leprosy infection

A CD40 variant is associated with systemic bone loss among patients with rheumatoid arthritis

Contact Info

Product

Resources

About