The role of ABCB1 gene polymorphisms in steroid-resistant nephrotic syndrome: Evidence from a meta-analysis of steroid-receiving patients

Abstract

Previous studies in nephrotic syndrome have shown that three common variants in the ABCB1 gene, including rs1128503, rs2032582, and rs1045642, change the expression and activity of ABCB1, which may be responsible for the drug resistance. However, as a result of the inconclusive outcomes of these studies, we performed a meta-analysis to validate the association between ABCB1 polymorphisms and the susceptibility of steroid-resistant nephrotic syndrome (SRNS). The association was evaluated by calculating the odds ratio (OR) and 95% confidence interval. A total of 12 studies containing 1,463 subjects (514 steroid-resistant and 949 steroid-sensitive) were included. Single nucleotide polymorphism rs1128503 showed a significant association with SRNS (p < 0.05) only in the allele model (OR = 1.40) in Africans. A statistically significant association was found for rs2032582 in codominant 2, dominant, recessive, and allele models (OR = 1.85, 1.52, 1.38, and 1.34, respectively). Subgroup analysis revealed that rs2032582 showed a significant correlation with SRNS in codominant 1, 2, dominant, over-dominant, and allele models in Africans (OR = 3.22, 3.52, 3.29, 1.74, and 1.83, respectively). In the case of rs1045642, codominant 1 (OR = 0.72) and recessive models (OR = 1.34) revealed a significant correlation with SRNS. Again, codominant 1 (OR = 0.58), dominant (OR = 0.69), and over-dominant models (OR = 0.62) showed a protective effect in Asians. Haplotype analysis showed that the TGC haplotype is associated with a 1.83, 1.77, and 2.17 times significant correlation in overall, Asian, and African populations, respectively. By contrast, the CGC haplotype showed a 0.69 and 0.57 times lower association in the overall and African populations, respectively. The CTC haplotype also showed a 1.79 times enhanced susceptibility for SRNS in the overall population. Our study suggests that ABCB1 polymorphisms are associated with SRNS development, especially in Africans and Asians.

Keywords: ABCB1; MDR1; nephrotic syndrome; polymorphisms; steroid resistance.