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.

Polymorphisms in drug metabolism genes predict the risk of refractory myasthenia gravis

“…MG is a multifactorial disease involving complex genegene and gene-environment interactions (34)(35)(36). No genegene interactions were identified among possible SNP combinations in GMDR analysis, but we cannot exclude the possibility of other multiple interactions that influence the therapeutic effects of MG. Several investigations suggested that MDR1, NR3C1, and FKBP5 polymorphisms may confer resistance to immunosuppressive therapy (37)(38)(39). The present study did not find any association between their genotypes and refractory MG. Further work targeting more diverse genotypes will be necessary.…”

Carnosine Potentiates Doxorubicin-Induced Cytotoxicity in Resistant NCI/ADR-RES Cells by Inhibiting P-Glycoprotein—In Silico and In Vitro Evidence

“…Resistance of the cancer cell to chemotherapy exaggerates the problem of increased cancer-associated mortality and morbidity [ 1 ]. The increased expression and activity of P-gp diminishes drug delivery to cellular targets and increases the MDR of cancers [ 2 , 4 , 5 ]. Indeed, clinical evidence implicates P-gp with therapy failure and poor prognosis [ 7 , 8 ].…”

“…The efflux of xenobiotics is a powerful mechanism leading to MDR during cancer chemotherapy [ 2 , 3 ]. Unfortunately, like many anticancer agents, doxorubicin suffers extrusion through the cell membrane by the action of P-gp [ 12 , 25 , 26 ], dramatically diminishing its efficacy.…”

“…Besides the lack of adequate therapies and late discovery in many cases, the development of multidrug resistance (MDR) contributes to this high mortality. One important mechanism by which cancer cells resist cytotoxic drugs is increasing the expression of specific efflux pumps that shuttle organic molecules to the outside of the cell across the plasma membrane, preventing their intracellular accumulation to cytotoxic levels and ultimately leading to therapeutic failure [ 2 , 3 ]. These transmembrane efflux pumps include P-glycoprotein (P-gp), a member of the ATP-binding cassette (ABC) family of transporters that are associated with cancer drug resistance [ 4 , 5 ].…”

“…The activity of the ABC family of transporters protects normal body cells from chemical insults by shuttling xenobiotic molecules across the cell membrane [ 6 ]. Contrarily, the expression and function of such transport systems largely determine the susceptibility of cancer cells to chemotherapeutic agents [ 2 , 3 ]. The increased expression and/or activity of P-gp, encoded in humans by the ABCB1 gene, confers resistance to anticancer drugs [ 4 , 5 ].…”