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. 2022 May:153:155851.
doi: 10.1016/j.cyto.2022.155851. Epub 2022 Mar 9.

Role of cytokines in multiple myeloma: IL-1RN and IL-4 VNTR polymorphisms

Istemi Serin  1 , Yasemin Oyaci  2 , Mustafa Pehlivan  3 , Sacide Pehlivan  2
Affiliations

Role of cytokines in multiple myeloma: IL-1RN and IL-4 VNTR polymorphisms

Istemi Serin et al. Cytokine. 2022 May.

Abstract

Introduction: The IL-1 receptor antagonist (IL-1Ra or IL-1RN) is a member of the IL-1 superfamily that functions as a competitive antagonist of the cell surface IL-1 receptor, thereby regulating various immune and inflammatory responses related to IL-1. IL-1 induces tumor growth and metastasis, while IL-1RN inhibits the secretion of IL-1α and IL-6 in cancer cells. Interleukin-4 (IL-4) is a potent anti-inflammatory cytokine, can be secreted by many types of immune cells. In this study, it was aimed to reveal the effects of IL-1RN and IL-4 VNTR polymorphisms on disease development and survival in patients with multiple myeloma (MM).

Material and methods: In this study, 244 patients diagnosed with MM in hematology clinic between January 2010 and January 2021, and 179 healthy individuals were included. The genotypes of the IL-1RN VNTR polymorphism were statistically compared before treatment between patients having undergone stem cell transplantation and healthy controls, as were the genotypes of IL-4 VNTR polymorphism. Additionally, the statistically significant effects of these genotypes on survival were examined.

Results: In the statistical analysis of the distribution of IL-1RN VNTR gene variants, 1/3 and 1/4 genotypes were found to be significantly higher in patients with MM compared to the healthy controls (p = 0.035). There was no significant difference between the MM patient group and the healthy controls in terms of IL-4 VNTR genotype distribution. PFS of patients with IL-1RN VNTR non-2-allele carrier genotypes was significantly shorter, but no significant effect was found on OS (p = 0.03, p = 0.786, respectively). Patients with IL-1RN VNTR non-2-allele carrier genotypes had 1.718-fold increased risk of shorter PFS.

Conclusions: In conclusion, with this study, the effects of IL-1RN VNTR and IL-4 VNTR polymorphisms on MM were evaluated for the first time in the literature. This study will shed light on ones on cytokine-MM relationship and epigenetic mechanisms.

Keywords: IL-1 receptor antagonist; IL-4; Multiple myeloma; Polymorphisms; Survival.

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