IL‐1A rs1800587, IL‐1B rs1143634 and IL‐1R1 rs2234650 polymorphisms in Iranian patients with systemic sclerosis

Abstract

Systemic Sclerosis (SSc) is a systemic autoimmune disorder, with ambiguous pathogenesis. Genetic and environmental factors were proved to be correlated with SSc aetiology. Single nucleotide polymorphisms (SNPs) in cytokine genes can alter the structure and function of the cytokines and consequently may increase the susceptibility to a specific disease. In this study, we investigated SNPs of the IL-1 gene cluster in Iranian SSc patients. We obtained blood samples from 170 SSc patients and 213 healthy individuals. Cytokine genotyping results were obtained by polymerase chain reaction with sequence-specific primers (PCR-SSP). IL-1A rs1800587, IL-1B rs1143634 and IL-1R1 rs2234650 were evaluated for SNP study. The frequency of the IL-1B rs1143634 CT genotype was significantly lower in SSc patients compared to the controls (OR = 0.584; 95% CI = 0.385-0.886; P-value = 0.023), so we propose that CT genotype of this allele might be protective. According to our haplotype analysis, CCC haplotype frequency is higher in the control group compared to SSc patients (OR = 1.575; 95% CI = 1.176-2.111; P-value = 0.008) and in contrast, CTC haplotype frequency is lower in the control group compared to SSc patients (OR = 0.152; 95% CI = 0.047-0.484; P-value = 0.002), so they might decrease and increase the susceptibility of having SSc, respectively. In addition, we reported two significant diplotypes frequency differences among SSc patients and healthy individuals. It is highly important that there is not much resemblance between the IL-1 gene cluster polymorphism in different populations, so we can indicate that SNPs may play critical roles when they are combined with other genetic and environmental factors.

The association of genetic polymorphisms in interleukin-1 receptors type 1 and type 2 with age-related hearing impairment in a Taiwanese population: a case control study

“…The association of SNPs with the disease may be organ specific. In an Iranian study, the authors reported that some haplotypes of SNPs IL-1A rs1800587, IL-1B rs1143634 and IL1R1 rs2234650 were associated with systemic sclerosis [22]. Another study found that the haplotype of three IL1R2 SNPs rs4141134, rs11674595, and rs7570441 was associated with an increased risk on depressive symptom trajectories in oncology patients and family caregivers [23].…”

Genetic implications in the pathogenesis of systemic sclerosis

“…IL‐1α and IL‐1β are mainly secreted by natural killer (NK) cells and macrophages as pro‐inflammatory cytokines. Among 3 variants of the IL1 gene family, IL1RN gene rs2234650 SNP, IL1A gene rs1800587 SNP and IL1B gene rs1143634 SNP, the IL1B gene rs1143634 CT acts as disease modulator . Based on haplotype evaluation, CCC haplotype increased the risk of SSc, whereas the CTC haplotype was protective .…”

“…Among 3 variants of the IL1 gene family, IL1RN gene rs2234650 SNP, IL1A gene rs1800587 SNP and IL1B gene rs1143634 SNP, the IL1B gene rs1143634 CT acts as disease modulator . Based on haplotype evaluation, CCC haplotype increased the risk of SSc, whereas the CTC haplotype was protective . Moreover, the role of peroxisome proliferator activated receptor gamma (PPAR‐γ) has been elucidated in the pathogenesis of SSc.…”

Interleukin 1α and 1β gene variations are associated with tuberculosis in silica exposed subjects

“…Besides silicosis, this polymorphism has been previously associated with the modulation of the severity of other inflammatory diseases, such as Hashimoto's thyroiditis, Graves’ disease, periodontitis, and rheumatoid arthritis . Second, the −889C/T (rs1800587) SNP is located in the 5′‐untranslated region (5′‐UTR) of the IL1A gene and plays an important role in the transcriptional regulation of the gene, leading to an increased serum protein level . This polymorphism was previously associated with periodontitis, sepsis, and allergic rhinitis .…”