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Background <p>Several studies have linked the development of steroid-resistant nephrotic syndrome (SRNS) to variations in the multidrug resistance 1 gene (<i>MDR1</i>). However, disparities in findings have been noted among children of different ethnic origins.</p> Objectives <p>This study aimed to examine the relationship between <i>MDR1</i> variants [rs944806668 (V1), rs1816042256 (V2), and rs1295312177 (V3)] and the risk of developing SRNS in Iraqi patients with idiopathic nephrotic syndrome (INS).</p> Methods <p>This case–control study included children with steroid-sensitive INS (<i>n</i> = 30) and SRNS (<i>n</i> = 30) from the Babylon Hospital for Maternity and Pediatrics. Sanger sequencing was used to determine the participants’ genotypes.</p> Results <p>Children with the V2 T/C genotype were more likely to develop SRNS [odds ratio (OR) and 95% confidence interval (95% CI): 10.8 (3.26–35.72), <i>p</i> &lt; 0.001] than those with the wild genotype. However, no significant association with steroid response was observed for the V1 genotypes and alleles [OR (95% CI): 0.58 (0.18–1.91) and 0.63 (0.21–1.9), respectively; <i>p</i> &gt; 0.05]. Moreover, children with the wild–variant–variant genotype combination of the V1, V2, and V3 variants exhibited a significantly higher risk of developing SRNS [OR (95% CI) 34 (4.91–235.61), <i>p</i> &lt; 0.001] than those with the wild–wild–wild genotype combination.</p> Conclusion <p>These findings highlight the need to incorporate pharmacogenetic screening into the clinical management of SRNS. Children with nephrosis having the V2 T/C and V3 A/T genotypes, whether individually or in combination, are likely to resist prednisolone therapy, implying the need for alternative therapeutic approaches. Further studies are required to elucidate the potential implications of <i>MDR1</i> variants for personalized drug therapy in children with INS.</p>

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Assessing the association of rare MDR1 variants (rs944806668, rs1816042256, and rs1295312177) with steroid response in Iraqi children with idiopathic nephrotic syndrome

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  • 发表日期：

    2025年2月18日

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  • Ali Mohammed Abd Alridha,
  • Dheyaa Jabbar Kadhim,
  • Ayad Hussein Ali Alkhazrajy

摘要

Background

Several studies have linked the development of steroid-resistant nephrotic syndrome (SRNS) to variations in the multidrug resistance 1 gene (MDR1). However, disparities in findings have been noted among children of different ethnic origins.

Objectives

This study aimed to examine the relationship between MDR1 variants [rs944806668 (V1), rs1816042256 (V2), and rs1295312177 (V3)] and the risk of developing SRNS in Iraqi patients with idiopathic nephrotic syndrome (INS).

Methods

This case–control study included children with steroid-sensitive INS (n = 30) and SRNS (n = 30) from the Babylon Hospital for Maternity and Pediatrics. Sanger sequencing was used to determine the participants’ genotypes.

Results

Children with the V2 T/C genotype were more likely to develop SRNS [odds ratio (OR) and 95% confidence interval (95% CI): 10.8 (3.26–35.72), p < 0.001] than those with the wild genotype. However, no significant association with steroid response was observed for the V1 genotypes and alleles [OR (95% CI): 0.58 (0.18–1.91) and 0.63 (0.21–1.9), respectively; p > 0.05]. Moreover, children with the wild–variant–variant genotype combination of the V1, V2, and V3 variants exhibited a significantly higher risk of developing SRNS [OR (95% CI) 34 (4.91–235.61), p < 0.001] than those with the wild–wild–wild genotype combination.

Conclusion

These findings highlight the need to incorporate pharmacogenetic screening into the clinical management of SRNS. Children with nephrosis having the V2 T/C and V3 A/T genotypes, whether individually or in combination, are likely to resist prednisolone therapy, implying the need for alternative therapeutic approaches. Further studies are required to elucidate the potential implications of MDR1 variants for personalized drug therapy in children with INS.