PRRC2A rs114580964 Variant as an Independent Predictor of Poor Kidney Prognosis in Chinese Patients with Lupus Nephritis

Background: Lupus nephritis (LN) is a significant manifestation of systemic lupus erythematosus (SLE) with profound immune complex deposition in the glomerulus. The prognosis of LN varies across ethnic groups, with Asian populations often exhibiting higher rates of renal involvement and poorer outcomes. In our prior genome-wide association study, the PRRC2A variant rs114580964 was identified as a novel genetic determinant for susceptibility to LN. However, the correlation between the rs114580964 variant and clinical outcomes as well as prognosis of LN remains unclear. Methods: This cohort study included 484 Chinese patients with LN in First Affiliated Hospital of Sun Yat-sen University. Clinical characteristics and outcomes were analyzed, with 469 patients included in the prognostic analysis after 15 patients were lost to follow-up. The primary outcome was the incidence of end-stage renal disease (ESRD). Results: Among 484 patients, 24 (5%) had the rs114580964-AA/AC genotype, while 460 (95%) had the rs114580964-CC genotype. Patients with the rs114580964-AA/AC genotype exhibited weaker mesangial IgM deposition, lower erythrocyte sedimentation rate (ESR), and lower IgA levels compared to those with the rs114580964-CC genotype. Kidney survival analysis indicated that the rs114580964-AA/AC genotype was associated with poorer long-term kidney outcomes in LN. Cox regression analysis identified the rs114580964-AA/AC genotype as an independent risk factor for kidney survival in LN patients. Conclusion: The PRRC2A rs114580964-AA/AC variant independently predicts poor kidney prognosis in Chinese patients with lupus nephritis.