INVESTIGATION OF THE EFFECT OF THSD7A LEVEL AND PLA2R1 POLYMORPHISM IN PATIENTS WITH MEMBRANOUS NEPHROPATHY

Elsa ALIAKBARI, Aida ADIKOZALOVA, Hayriye SENTURK ÇIFTÇI, Sonay TEMURHAN, Halil YAZICI, Çiğdem KEKIK ÇINAR

Turkish Journal of Nephrology - 2026;35(3):202-207

İstanbul University Institute of Graduate Studies in Health Sciences, İstanbul, Türkiye

 

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.