Abstract
Aims This study is aimed at exploring the relation between IL-33 single-nucleotide polymorphisms (SNPs) and the risk of systemic lupus erythematosus (SLE). Methods SNPStats (online software) was used to test the Hardy-Weinberg equilibrium in controls. Generalized multifactor dimensionality reduction (GMDR) was adopted to screen the preferable interaction between IL-33 SNPs and current smoking. Results Logistic regression analysis based on the fundamental data of age, gender, BMI, current smoking, and alcohol drinking showed that both rs1929992-G and rs1891385-C alleles were correlated with an increasing risk of SLE, the ORs (95% CI) of which were 1.62 (1.21-2.05) and 1.64 (1.22-2.10), respectively. One two-locus model (rs1929992×current smoking) had a testing accuracy of 60.11% (P = 0.0010). Through an overall multidimensional model, optimum cross-validation consistency was obtained. The analysis indicated that current smoking status influenced the SLE risk depending on the genotypes at rs1929992. Pairwise LD analysis indicated that haplotype rs1929992G-rs7044343T was statistically related to the elevating risk of SLE (P < 0.05). Those subjects with the G-T haplotype had a higher SLE risk than those with other haplotypes, after correction with factors, including gender, alcohol drinking, age, BMI, and current smoking. Conclusions The rs1929992-G and rs1891385-C allele, interaction between the rs1929992 gene and current smoking, and haplotype rs1929992G-rs7044343T were all risk factors of SLE.
Highlights
Systemic lupus erythematosus (SLE) represents a universal type of autoimmune rheumatic diseases
Those subjects with the G-T haplotype had a higher SLE risk than those with other haplotypes; after factors including age, BMI, current smoking, gender, and alcohol drinking were excluded. We showed that both the rs1929992-G and rs1891385-C alleles were correlated to the risk of SLE and presented as potential risk factors for developing SLE
Li et al [19] for the first time found the significance of IL-33 rs7044343 in the development of RA, while the CC genotype of rs7044343 has been linked to the downregulation of serum IL-33 levels
Summary
Systemic lupus erythematosus (SLE) represents a universal type of autoimmune rheumatic diseases. It is featured as the dysfunction of T cell response and B cell activation that leads to the generation of immune complexes in a variety of organs and tissues, which predominantly occurs in young and middle-aged females [1, 2]. Several articles unraveled the correlation between IL-33 gene polymorphisms and autoimmune diseases, such as ankylosing spondylitis, Behçet’s disease, and lupus [11,12,13], and these studies all presented strong susceptibility. Our study is aimed at examining the role of IL-33 SNPs, as well as its interaction with the environment to the susceptibility to SLE in Chinese population
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