Photo Credit: Rasi Bhadramani
The following is a summary of “Distinct genetic risk loci between biopsy-proven renal and non-renal lupus: a 10-year longitudinal cohort,” published in the January 2025 issue of Rheumatology by Chan et al.
Systemic lupus erythematosus (SLE) presents as diverse subphenotypes, including lupus nephritis (LN). Previous studies linking genetic risk to LN were limited by cross-sectional data and imprecise subphenotyping.
Researchers conducted a retrospective study to explore the genetic basis of LN using a longitudinal cohort of distinctly subphenotyped patients.
They recruited patients with SLE with biopsy-proven LN or no renal involvement for at least 10 years never developed LN (NLN) from 8 centers. The genotyping of 230 SLE-associated SNPs was performed, and polygenic risk scores (PRS) were calculated. Genome-wide association analyses were conducted for LN-vs-control, NLN-vs-control, and LN-vs-NLN comparisons.
The results showed that among 1,462 patients, 824 (56%) had LN and 638 (43%) had NLN. PRS was significantly higher in the LN cohort. Genome-wide significant variants were identified in HLA, TNFAIP3, BLK, and STAT4 loci for LN, with STAT4 also significant for NLN. No statistically significant variants were found in LN-vs-NLN associations, but heterogeneity tests revealed loci including ELF1, OX40, DUSP22, and TPCN2.
Investigators identified distinct genetic risk loci associated with biopsy-proven LN, suggesting varying genetic predispositions for different SLE subphenotypes. The findings highlighted the importance of precise subphenotyping and longitudinal data in uncovering these genetic risks.
Source: academic.oup.com/rheumatology/advance-article-abstract/doi/10.1093/rheumatology/keaf027/7964735
