Investigation of the Effect of THSD7A Level and PLA2R1 Polymorphism in Patients with Membranous Nephropathy

Background: Membranous nephropathy (MN) is a glomerular disease characterized by subepithelial immune complex deposition and proteinuria. While phospholipase A2 receptor (PLA2R1) is the main autoantigen in idiopathic MN, thrombospondin type-1 domain-containing 7A (THSD7A) has also been implicated in a subset of patients. This study aims to evaluate the diagnostic and prognostic significance of serum THSD7A levels and PLA2R1 rs4664308 gene polymorphism in Turkish patients with MN.

Methods: Seventy biopsy-confirmed MN patients and 81 healthy controls were enrolled. Serum THSD7A levels were measured using enzyme-linked immunosorbent assay (ELISA), and rs4664308 genotyping was performed by TaqMan real-time polymerase chain reaction (PCR). Associations between THSD7A levels, genotypes, and clinical variables were analyzed using appropriate statistical methods. Receiver-operating characteristic (ROC) analysis was conducted to assess the diagnostic performance of THSD7A.

Results: Serum THSD7A levels were significantly higher in MN patients compared with controls (P = .016); however, ROC analysis demonstrated limited diagnostic value (area under the curve (AUC) = 0.671, sensitivity 70.6%, specificity 42.4%). The THSD7A levels showed no correlation with proteinuria, serum creatinine, estimated glomerular filtration rate, or blood pressure. The rs4664308 AA genotype and A allele were significantly more frequent in MN patients, whereas the AG genotype and G allele were more common in healthy controls (P < .001 and P = .004, respectively). No association was observed between rs4664308 genotypes and serum THSD7A concentrations.

Conclusion: Although serum THSD7A levels were elevated in MN patients, their limited diagnostic performance restricts their utility as standalone biomarkers. In contrast, the rs4664308 AA genotype and A allele were strongly associated with MN risk, suggesting potential value as genetic markers. Further studies are needed to confirm these findings and evaluate their prognostic significance.

Cite this article as: Aliakbari E, Adikozalova A, Senturk Ciftci H, Temurhan S, Yazici H, Kekik Cinar C. Investigation of the effect of THSD7A level and PLA2R1 polymorphism in patients with membranous nephropathy. Turk J Nephrol. 2026;35(3):202-207.