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.

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Huazhong University of Science and Technology