Association between IL1B polymorphisms and the risk of rheumatoid arthritis
Introduction
Rheumatoid arthritis (RA) is a common autoimmune disease in the clinic that is characterized by chronic synovitis, articular cartilage and bone destruction, joint deformity and loss of function. RA can cause painful stiffness and has a prolonged disease period. Movement impairment caused by arthritis can lead to physical and mental exhaustion, but there is no reliable treatment. RA incidence is approximately 1% in the total population; the incidence in females is significantly higher than that in males [1], [2]. The incidence of RA is considered to be the result of the combined action of genetic factors and environmental factors, but the specific mechanism remains unclear. Studies have shown that approximately 60% of RA risk is due to genetic factors [3]. Thus, we attempted to define genetic abnormalities associated with RA, as these may lead to more effective treatment strategies and a better understanding of risk prediction.
Early biomarkers can be found through genetic research, which can not only predict the occurrence of RA but also prevent the occurrence of inflammation, and ultimately achieve the goal of improving the quality of life of patients. Single nucleotide polymorphisms (SNPs) are a third-generation molecular marker. There are two main functions of SNPs: first, SNPs directly lead to changes in gene transcription level, translation level or protein function, thus leading to a disease or phenotype. Second, an SNP can be a genetic marker closely related to a disease or phenotype. Previous studies have shown that members of the interleukin cytokine family play a significant role in RA, such as IL-1 [4], IL-6 [5], IL-9 [6] and other factors.
The IL1B gene encodes the pro-inflammatory cytokine interleukin-1 (IL-1), a member of the IL-1 family that plays an important role in a variety of cell types, such as blood monocytes, macrophages, and cells of the central nervous system [7]. IL1B has been found to mediate chronic inflammatory responses in many diseases, such as neurodegenerative disease, Parkinson's disease [8], amyotrophic lateral sclerosis [9], essential tremor [10], Alzheimer’s disease [11] and inflammatory diseases [12]. Studies have shown that IL-1 blockers improve arthritis in mouse models and that IL-1 blockers have been confirmed in clinical trials to relieve rheumatoid arthritis in humans [13]. In vitro and in vivo trials have also shown that IL-1 beta significantly affects cartilage destruction and bone resorption [14], [15], [16]. Studies on IL1B gene polymorphisms have been carried out worldwide, but there are few studies of the correlation between the IL1B polymorphisms and the susceptibility to RA in China.
In this study, we investigated four SNPs, rs2853550, rs1143643, rs3136558 and rs16944, of the IL1B gene. We observed the relationship of these SNPs with RA susceptibility in Chinese Han population. Our research might provide more vital evidence for further elucidating the pathogenesis of RA.
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Study subjects
We randomly recruited 508 RA patients and 494 unrelated healthy controls at 630 Rheumatic Hospital in Xi'an and conducted the study. After pathological diagnosis by a physician, all patients were confirmed as having RA. The control group was healthy subjects matched in age and sex without any inflammatory bone and/or joint diseases or other conditions. The subjects were ethnic Han Chinese who were genetically unrelated.
SNP genotyping
Based on the USCS database and previous studies, we selected four
Results
The mean age was 59.00 ± 9.83 years in the patients and 51.16 ± 11.49 years in the controls (Table 1). In this study, the age distribution was matched between the case group and the control group (p > 0.05). To evaluate the function of the selected SNPs, we used HaploReg4.1 to annotate the functions of SNPs in IL-1B to reveal the potential associations between these SNPs and RA risk. The results showed that these SNPs were involved in the regulation of promoter/enhancer histone markers, DNase,
Discussion
The purpose of this research was to explore the correlations of IL-1B gene polymorphisms with RA susceptibility. Our findings suggested that polymorphisms of rs2853550, rs1143643 and rs16944 of IL-1B might be significantly correlated with RA susceptibility.
Cytokines play a key role in intercellular communication, immunity and inflammation as cellular signaling molecules. IL-1β is a major inflammatory immune response inducer and combines with the same cell surface receptors, leading to an
Conclusions
In summary, our findings showed a relationship between IL-1B polymorphisms and the increased risk of RA in a Chinese Northwest Han male population, which might provide a potential theoretical basis for the study of RA.
Ethics approval and consent to participate
This study has been approved by the Ethics Committee of Xi'an 630 Rheumatology Hospital. All procedures performed in this study conform to the ethical standards of the Institutional Research Board and the ethical standards of the Helsinki Declaration and its subsequent amendments. All participants were informed of the research procedures and purpose by the researchers and voluntarily signed informed consent.
Funding
This work was supported by the National Natural Science Foundation of China [8196029].
CRediT authorship contribution statement
Hao Rong: Data curation, Formal analysis, Writing - original draft. Xue He: Investigation, Methodology. Li Wang: Project administration. Mei Bai: Resources. Tianbo Jin: Software, Supervision. Yuhe Wang: Writing - review & editing. Wei Yang: Writing - review & editing. Yongjun He: Validation. Dongya Yuan: Conceptualization.
Declaration of Competing Interest
All authors state that they have no conflicts of interest.
Acknowledgments
We thank all participants who agreed to provide blood samples and the hospital staff who cooperated with our study.
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