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Low heterozygosity for rs3811050, a 5 prime untranslated region variant of the gene encoding interleukin-38 (IL1F10), is associated with a reduced risk of systemic lupus erythematosus
Abstract<sec> <title>Background

Interleukin-38 (IL-38), an inflammatory cytokine discovered in recent years, has been implicated in the pathogenesis of systemic lupus erythematosus (SLE). IL-38 is encoded by the IL1F10 (interleukin 1 family member 10) gene. Genetic variants of this gene have been associated with susceptibility to a number of autoimmune and inflammatory diseases, while their association with SLE risk has not been explored. In this case–control study, two novel variants of the 5 prime untranslated region (5′UTR) of the IL1F10 gene, rs3811050 C/T and rs3811051 T/G, were investigated in 120 women with SLE and 120 age-matched control women. The TaqMan allelic discrimination assay was used for genotyping of rs3811050 and rs3811051.

Results

The frequency of the rs3811050 CT genotype was significantly lower in SLE patients compared to controls (30.8 vs. 50.0%; odds ratio = 0.49; 95% confidence interval = 0.28–0.86; corrected probability = 0.045). The rs3811051 genotype frequencies did not show significant differences between patients and controls. Rs3811050 and rs3811051 showed weak linkage disequilibrium (LD) as indicated by the estimated LD coefficient and correlation coefficient values (0.32 and 0.05, respectively), and two-locus haplotype analysis revealed no significant differences between patients and controls. The frequencies of the rs3811050 T allele (38.8 vs. 20.6%; probability = 0.029) and the rs3811051 G allele (56.3 vs. 38.2%; probability = 0.038) were significantly higher in patients with mild/moderate disease activity than in patients with high disease activity, but significance was not maintained after applying Bonferroni correction (corrected probability = 0.058 and 0.076, respectively). Serum IL-38 concentrations (median and interquartile range) were significantly decreased in patients compared with controls (69.5 [64.1–74.8] vs. 73.5 [66.1–82.9] pg/mL; probability = 0.03), but were not influenced by SNP genotypes.

Conclusions

The heterozygous genotype of rs3811050, a 5'UTR variant, of the IL-38 encoding gene, IL1F10, is associated with a reduced risk of SLE among women. Furthermore, the rs3811050 T and rs3811051 G alleles may influence disease activity. In addition, serum IL-38 concentrations were down-regulated in SLE patients but were not affected by the rs3811050 and rs3811051 genotypes.

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