Novel variants in ARID1B, SPSB1, and RAET1-AS shape genetic susceptibility and protection in systemic lupus erythematosus and lupus nephritis.

BACKGROUND

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by immune dysregulation affecting multiple organs, most notably lupus nephritis (LN). Genetic susceptibility significantly contributes to disease severity and prognosis. However, genomic studies specific to Taiwanese SLE patients, particularly those focusing on LN, remain limited. This study aimed to identify genetic variants associated with SLE and LN in a Taiwanese cohort.

METHODS

Genome-wide association studies (GWAS) were performed on 276 Taiwanese SLE patients compared with 3393 patients with other rheumatic diseases. Single-nucleotide polymorphism (SNP) genotyping was conducted using the Taiwan Precision Medicine Array, with analyses adjusted for age, sex, and population structure. Functional annotations and biomarkers of renal function were assessed for identified SNPs.

RESULTS

Compared with patients with other rheumatic diseases, a novel protective variant, rs9480438 (ARID1B), was identified in the SLE group, suggesting an association with dysregulation of cell cycle checkpoints. In the LN group, a protective variant, rs1294028 (SPSB1), and a risk variant, rs17079029 (RAET1-G/RAET1-AS), were linked to altered serum biomarkers and potential pathogenesis influenced by TGFβ and NK cells.

CONCLUSIONS

Novel genetic variants related to immune regulation and autoimmunity in Taiwanese SLE and LN patients were identified. These variants provide insight into disease mechanisms and may guide early detection and personalized therapeutic approaches.