Genetic variants related to systemic lupus erythematosus revealed using bioinformatics

Abstract

Objectives Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organs and is characterized by immune inflammation. The pathogenesis of SLE is complex and involves genetic and environmental components. Methods In this study, single nucleotide polymorphisms (SNPs) closely related to SLE were searched through integration analysis of public gene expression profiles from Gene Expression Omnibus and European Bioinformatics Institute data, and immunochip data in a genome-wide association study. Results SLE-associated SNPs were identified in 17 genes common among datasets. The mRNA expression levels of three genes among them were verified to differ between SLE patients and healthy controls subjects based on real-time polymerase chain reaction and sequencing of peripheral blood mononuclear cells (PBMCs). The GG genotype frequency of rs116253043 in LY6G6D was significantly lower in SLE patients and the GC genotype frequency of rs328 on LPL was significantly higher in SLE patients than in controls. VARS2 levels were significantly higher in SLE PBMCs than controls, but there was no significant difference in allele or genotype frequencies of the two SNPs (rs115470445 [C/T] and rs114394807 [A/G]) between groups. Conclusion Our results suggest that the GG genotype of rs116253043 plays a protective role against SLE, whereas the C allele of rs328 is a risk factor for SLE and rs116253043 with the GC genotype is an SLE-susceptibility SNP.