Background Avascular necrosis (AVN) incompletely understood genetic architecture in patients with systemic lupus erythematosus (SLE). The aims of this study were to investigate genetic risk factors, biological and functional pathways associated with the risk of AVN in a large SLE cohort in Korea.

Methods Patients with SLE were enrolled in the Hanyang BAE Lupus cohort, in whom damage was measured annually according to the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). We conducted an association study to determine genetic risk factors for AVN in 612 SLE cases that genotyped by high-density immune-loci genotyping array (Immunochip) and genome-wide association study (GWAS) using Illumina HumanOmni1-Quad array.

Results Symptomatic AVN was the most common type of musculoskeletal damage (14.2%, n=87) among 612 SLE patients in Korea. In analysis of clinical factors, use of a high cumulative corticosteroid dose (OR 3.62, p=0.015) significantly increased the risk of AVN in multivariable analysis. We found the top 10 single-nucleotide polymorphisms (SNPs) associated with AVN (p<5.0×106) in SLE patients with AVN after adjusting for age, sex, disease duration, total cumulative corticosteroid dose, and top 10 PCs as covariates. In further analysis of SLE patients with AVN compared with SLE patients without AVN treated by a high corticosteroid [cumulative dose >20 g], the AVN-risk loci were highly expressed in fibroblasts (p=8.78×105) and musculoskeletal system (p=1.13×104) using DEPICT.

Conclusions These findings provide genetic evidence that pathway of fibroblasts are relevant to osteonecrosis. Individual genetic risk for the development of AVN should be assessed prior to treatment for SLE.

Funding Source(s): None