Clinical Value of ABCB1 and PAI-1 Gene Polymorphisms in Predicting Glucocorticoid-induced Adverse Reactions in Nephrotic Syndrome Patients

Abstract

Objective: Glucocorticoid (GC)-induced adverse reactions (ARs) have been extensively studied due to their potential impact on patients' health. This study aimed to examine the potential correlation between two polymorphisms [adenosine triphosphate-binding cassette B1 (ABCB1) C3435T and plasminogen activator inhibitor-1 (PAI-1) 4G/5G] and various GC-induced ARs in nephrotic syndrome (NS) patients.

Methods: In this study, 513 NS patients who underwent GC treatment were enrolled. Then, the patients were divided into two groups based on ABCB1 C3435T and PAI-1 4G/5G genotyping, and intergroup comparisons of clinicopathological data and GC-induced ARs were performed. Univariate and multivariate logistic analyses were subsequently conducted to identify potential risk factors for GC-induced ARs, and a nomogram was subsequently established and validated via the area under the ROC curve (AUC), calibration curve and decision curve analysis (DCA).

Results: We identified ABCB1 C3435T as an independent risk factor for the development of steroid-associated avascular necrosis of the femoral head (SANFH) (OR: 2.191, 95% CI: 1.258-3.813, P=0.006) but not as a risk factor for the occurrence of steroid diabetes mellitus (S-DM). On the other hand, PAI-1 4G/5G was identified as an independent risk factor for the development of both SANFH (OR: 2.198, 95% CI: 1.267-3.812, P=0.005) and S-DM (OR: 2.080, 95% CI: 1.166-3.711, P=0.013). Notably, no significant correlation was found between the two gene polymorphisms and other GC-induced ARs. In addition, two nomograms were established and validated to demonstrate strong calibration capability and clinical utility.

Conclusion: Assessing ABCB1 C3435T and PAI-1 4G/5G before steroid treatment in NS patients could be useful for identifying patients at a high risk of developing SANFH and S-DM.

Keywords: adenosine triphosphate-binding cassette B1; nephrotic syndrome; plasminogen activator inhibitor-1; steroid diabetes; steroid-associated avascular necrosis of the femoral head.