4.4 Article

Genetic polymorphisms influence the steroid treatment of children with idiopathic nephrotic syndrome

Journal

PEDIATRIC NEPHROLOGY
Volume 27, Issue 9, Pages 1511-1517

Publisher

SPRINGER
DOI: 10.1007/s00467-012-2182-0

Keywords

Idiopathic nephrotic syndrome; Steroid; CYP3A5; ABCB1; Polymorphism

Funding

  1. Kaohsiung Veterans General Hospital, Taiwan, Republic of China [VGHKS98-085]

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Idiopathic nephrotic syndrome (INS) is the most frequent type of nephrotic syndrome that occurs in children. Its response to treatment with steroids varies. The aim of this study was to analyze the correlation between steroid metabolism-related genes and the response to steroid treatment. The patient cohort comprised 74 children with INS, of whom were 58 steroid-sensitive (SS) cases and 16 steroid-resistant (SR) cases. The genetic polymorphisms analyzed were those of the CYP3A5 gene (A6986G) and ABCB1 gene (C1236T, G2677T/A, and C3435T), and the polymorphisms between SS and SR children were compared. C1236T in ABCB1 was associated with steroid resistance in INS children [odds ratio (OR) 2.65, 95 % confidence interval (CI) 1.01-6.94; p = 0.042] The frequency of the T allele was significantly higher in SR subjects than in SS subjects (0.81 vs. 0.62, respectively). A6986G in CYP3A5 showed a trend of association, but this association did not reach statistical significance (OR 2.63, 95 % CI 0.94-7.37; p = 0.059). No significant correlation was found between treatment response and G2677T/A or C3435T in ABCB1. Our results indicate that among our pediatric patients with INS the C1236T polymorphism in the ABCB1 gene was associated with steroid resistance, while the A6986G polymorphism in the CYP3A5 gene showed a trend of association, but did not reach statistical significance, requiring further analysis.

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