Interleukin-2 and Interleukin-8 Gene Polymorphisms and Acquired Aplastic Anemia Risk in a Chinese Population

Abstract

Background/Aims: Cytokines IL-2 and IL-8 both participate in immune regulation. However, the relationship between polymorphisms in these two cytokines and the risk of acquired aplastic anemia (acquired AA) has not been explored. Methods: We selected five SNPs including rs11575812, rs2069772 and rs2069762 of IL-2, rs2227306 and rs2227543 of IL-8. SNaPshot genotyping was used to test the genotypes of IL-2 and IL-8 polymorphisms in a population of 101 acquired AA patients and 165 healthy controls. Results: The rs2069762 G allele appeared to be a protective mutation, but no significant differences were found in other four SNPs. We also found that rs2069762 had an impact on the transcriptional regulation. Conclusions: It could be assumed that the rs2069762 polymorphism might reduce the risk of acquired aplastic anemia, while the remaining four SNPs might not contribute to susceptibility to acquired AA in a Chinese population.

Aplastic anemia, cellular and molecular aspects

“…IL‐2 is markedly elevated in the BM and peripheral blood of patients with acquired AA. There are also high levels of IL‐6 and IL‐8 in these patients, its level is related to the severity of the disease and the highest rate is observed in patients with very severe aplastic anemia (VSAA) (Gupta et al, 2017; Zhang et al, 2017). Elevated serum INF‐γ levels are present in approximately 30% of AA patients and the BM of most of these patients (De et al, 2019).…”

“…G allele and GG genotype of IL23R‐rs11209032 are associated with better IST results in AA patients, and in contrast, the GG genotype of STAT3‐rs744166 is associated with IST deficiency in these patients (Zhao et al, 2018). The rs2069762 IL2‐T>G mutation may be associated with a reduced risk of AA, and the mutant type of homozygous GG and the G allele for CTLA‐4‐rs231775 may be associated with an increased risk (Li et al, 2016; Zhang et al, 2017).…”

“…The prevalence of this disease is due to exposure to different environmental conditions such as the use of certain drugs and chemicals or infectious agents such as viruses and bacteria. The genetic background of different racial populations may also change the risk of developing the disease; however, the exact pathogenesis of acquired AA is still unclear (Adhikari & Mandal, 2019; Park et al, 2015; Zeng & Katsanis, 2015; Zhang et al, 2017). Hematopoietic stem cells (HSCs) niche, which includes osteoblastic, vascular, and perivascular niches, are impaired in this disease.…”

“…Immunosuppressive therapies (ISTs) and allogeneic stem cell transplants can be helpful, but the response to treatment depends on the severity of the disease, age, and the choice of initial treatment. Since the two‐thirds of patients with acquired AA can improve their hematopoietic function after ISTs, AA can be classified as an autoimmune disease (Scheinberg & Young, 2012; Zhang et al, 2017). In this study, the effect of signaling pathways, cytokines, chemokines and the immune system on the development and progression of AA and the effect of this disease on HSCs niche, and, its changes during this disease will be investigated.…”