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

Bagheri-Hosseinabadi, Zahra; Mirzaei, Mohammad Reza; Aliakbari, Mina; Abbasifard, Mitra

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.

SYSTEMIC lupus erythematosus; GENETIC polymorphisms; INFLAMMATORY mediators; MONONUCLEAR leukocytes; SINGLE nucleotide polymorphisms; GENE expression; CYTOTOXIC T lymphocyte-associated molecule-4

Clinical Rheumatology, 2023, Vol 42, Issue 8, p2187

0770-3198

Academic Journal

10.1007/s10067-023-06575-y