Objective  To explore the interaction between 1,25-hydroxyvitamin D3 25-（OH）D3 and M-type phospholipase A2 receptor 1 （PLA2R1） gene polymorphism in the progression of idiopathic membranous nephropathy （IMN）.

Methods  A total of 101 hospitalized IMN patients from January 2019 to January 2023 were selected for this prospective study. They were assigned into two groups of recurrence and non-recurrence according to whether or not relapse occured within 6 months. Baseline profiles, 25-（OH）D3 level and PLA2R1 gene polymorphism were compared between two groups. Logistic regression was utilized for examining the influencing factors of IMN progression. And interaction coefficient γ and OR values were employed for analyzing the interaction effects of 25-（OH）D3 and PLA2R1 gene polymorphism on IMN progression.

Results  The level of uric acid was higher in recurrence group than that in non-recurrence group （419.36 ± 25.44）μmol/L vs （366.20 ± 28.34）μmol/L while 25-（OH）D3 level was lower than that in non-recurrence group （33.60 ± 10.74）nmol/L vs （42.40 ± 9.56）nmol/L, P＜0.05. The proportion of patients with AA genotype at rs4664308 locus was higher in recurrence group than that in non-recurrence group （69.44% vs 44.62%） while the proportions of patients with GA genotype （27.78% vs 43.08%） and GG genotype （2.78% vs 12.31%） were lower than those in non-recurrent group （P＜0.05）. Logistic regression analysis revealed that uric acid, 25-（OH）D3, GA and AA genotypes at rs4664308 were correlated with the progression of IMN （P＜0.05）; the risk of progression spiked by 4.233 folds for each unit of uric acid increase. For each unit reduction of 25-（OH）D3, the risk of disease progression increased by 0.581 fold. The risk of disease progression in GA and AA genotype rs4664308 patients was 3.253 and 4.054 folds higher than that in GG genotype ones. Interaction analysis showed that OR values of interaction between 25-（OH）D3 and PLA2R1 gene polymorphisms were ＜ product of OR values of two genes alone and the effects of two genes on the progression of IMN were in line with sub-multiplication model and interaction coefficient γ was ＞1. Abnormal 25-（OH）D3 had a positive interaction with PLA2R1 gene polymorphism （P＜0.05）.

Conclusion  25-（OH）D3 and PLA2R1 gene polymorphisms are correlated with disease progression in IMN patients. And 25-（OH）D3 level has a positive interaction on the effect of PLA2R1 gene polymorphism, and combined detection may help to predict the risk of disease progression and provide decision-making support for personalized preventive interventions.