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Association of interleukin 33 gene polymorphisms with susceptibility and regulation of inflammatory mediators in Systemic lupus erythematosus patients

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Abstract

Background

Studies have indicated the involvement of interleukin (IL)-33 in the pathogenesis of Systemic lupus erythematosus (SLE). This research intended to evaluate the association of IL33 gene rs1929992 and rs7044343 Single nucleotide polymorphisms (SNPs) with risk of SLE. In addition, the association between these SNPs and inflammatory cytokines was determined.

Methods

In this study, 200 SLE cases and 200 healthy subjects were recruited. Using allelic discrimination Real-time PCR, IL33 gene rs1929992 and rs7044343 SNPs were genotyped. The mRNA expression levels of IL-1β, IL-6, IL-33, TNF-α were determined in the peripheral blood mononuclear cells (PBMCs). The serum levels of cytokines were also measured.

Results

The G allele (OR = 1.57, CI: 1.18–2.08, P = 0.0017), GG genotype (OR = 2.52, CI: 1.33–4.77, P = 0.0043), and GA genotype (OR = 2.12, CI: 1.34–3.34, P = 0.0011) of rs1929992 SNP was significantly associated with an increased SLE risk. The C allele (OR = 1.44, CI: 1.08-1.90; P = 0.0105), CC genotype (OR = 2.07, CI: 1.15-3.71; P = 0.0146), and CT genotype (OR = 1.61, CI: 1.02-2.53, P = 0.0395) of rs7044343 was significantly associated with increased SLE risk. The PBMC mRNA expression and serum levels of IL-1β, IL-6, IL-33, TNF-α were significantly increased in the SLE patients compared to controls. However, there was no significant difference in the mRNA expression and serum levels of IL-1β, IL-6, IL-33, and TNF-α among the SLE patients with three genotypes for both rs1929992 and rs7044343 polymorphisms.

Conclusions

IL33 gene rs1929992 and rs7044343 SNPs are involved in SLE pathogenesis but they might not influence on the inflammatory pathway.

Key Points

• The alleles and genotypes of IL33 gene rs1929992 and rs7044343 SNPs were significantly associated with an increased SLE risk.

• The mRNA expression and serum levels of IL-1β, IL-6, IL-33, TNF-α were significantly increased in the SLE patients compared to controls.

• There was no significant association of mRNA expression and serum levels of inflammatory cytokines with IL33 SNPs in the SLE patients.

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Data availability

All data that support the conclusions of this manuscript are included within the article.

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Acknowledgements

The authors are grateful of the patients for their participation in this study.

Funding

This article was supported by a grant from Deputy of Research, Rafsanjan University of Medical Sciences.

Author information

Authors and Affiliations

  1. Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran

    Zahra Bagheri-Hosseinabadi & Mohammad Reza Mirzaei

  2. Department of Clinical Biochemistry, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran

    Zahra Bagheri-Hosseinabadi & Mohammad Reza Mirzaei

  3. Student Research Committee, Rafsanjan University of Medical Sciences, Rafsanjan, Iran

    Mina Aliakbari

  4. Immunology of Infectious Diseases Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran

    Mitra Abbasifard

  5. Department of Internal Medicine, Ali-Ibn Abi-Talib Hospital, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran

    Mitra Abbasifard

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  1. Zahra Bagheri-Hosseinabadi
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  3. Mina Aliakbari
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Contributions

Zahra Bagheri-Hosseinabadi performed experiments, participated in manuscript writing, and read the manuscript critically. Mohammad Reza Mirzaei participated in performing experiments, performed statistical analysis, participated in manuscript writing, and read the manuscript critically. Mina Aliakbari participated in performing experiments, performed statistical analysis, participated in manuscript writing, and read the manuscript critically. Mitra Abbasifard developed the main idea, participated in study conceptualization, participated in manuscript writing, and read the manuscript critically.

Corresponding author

Correspondence to Mitra Abbasifard.

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Ethics approval and consent to participate

This study was approved by the ethics committee of Rafsanjan University of Medical Sciences (IR.RUMS.REC.1400.172) and all individuals voluntarily signed a written informed consent form. All methods were performed in accordance with the relevant guidelines and regulations by Rafsanjan University of Medical Sciences.

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Bagheri-Hosseinabadi, Z., Mirzaei, M.R., Aliakbari, M. et al. Association of interleukin 33 gene polymorphisms with susceptibility and regulation of inflammatory mediators in Systemic lupus erythematosus patients. Clin Rheumatol 42, 2187–2197 (2023). https://doi.org/10.1007/s10067-023-06575-y

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