MDR-1 gene polymorphisms in steroid-responsive versus steroid-resistant nephrotic syndrome in children

Jafar, Tabrez; Prasad, Narayan; Agarwal, Vikas; Mahdi, Abbas Ali; Gupta, Amit; Sharma, Raj Kumar; Negi, Mahendra Pal Singh; Agrawal, Suraksha

doi:10.1093/ndt/gfr150

Cited by 42 publications

(53 citation statements)

References 25 publications

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“…We also found that the SNP C3435T variations were high among patients on compare with healthy children. In this study, distribution of C3435T, CC, CT, and TT genotype frequency is close to that in the Asians such as Japanese, Chinese, and Indian population [26]. In this study, the genotypic distribution of CT, TT, and CC was relatively high on compare with controls were as are showed C3435T, CT, CC, and TT genotype (Figs.…”

Section: Discussionsupporting

confidence: 78%

IDENTIFICATION OF FUNCTIONAL SNPs OF MDR1 GENE AMONG NEPHROTIC SYNDROME CHILDREN IN SOUTH INDIA

Arumugam

2017

Asian J Pharm Clin Res

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Objective: This study was conducted to determine the frequency of C3435T and G2677T/C single nucleotide polymorphisms of multi drug resistance gene -1 (MDR1) in nephrotic syndrome (NS) children in relation to healthy subjects. The role and association of these SNPs were also determined, whether response and/or resistance to steroid treatment in children with NS in south India. Methods:Genomic DNA was isolated from 371 blood samples collected from children with NS and controls. Among 173 cases, categorized into steroid-resistant NS (SRNS) were 90 and steroid-sensitive NS (SSNS) were 83 and 198 blood samples were included as controls. All samples were subjected to DNA extraction, and polymerase chain reaction followed by restriction fragment length polymorphism for identification of C3435T and G2677T/C genomic variations. Results:The frequencies of MDR-1 C3435T, CT, TT, and CC genotypes and SNP G2677T/C GG and G allele genotypes were observed in this study group. In SRNS, children showed significantly higher frequencies of MDR-1 C3435T, CT, TT, and TT+CC genotypes were observed than SRNS and controls. The allele frequencies of SRNS children showed CC -4%, CT -32% and TT -12% and in SSNS children, CC -10.98%, CT -27.2% and TT -13.9% were observed. Furthermore, increased frequencies of MDR-1 C3435T CT, TT, TT+CC genotypes, or T allele were observed in children aged <9 years old. There were no different genotype and allele frequency observed in G2677T/C genotypes NS children and controls. Conclusion:Based on these data, we are suggesting that MDR-1 C3435T gene polymorphisms are risk factors of increased susceptibility, earlier onset of NS as well as leads to steroid resistance. Whereas SNP G2677T/C gene polymorphisms do not have significant role observed in this study population.

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Section: Discussionsupporting

confidence: 78%

IDENTIFICATION OF FUNCTIONAL SNPs OF MDR1 GENE AMONG NEPHROTIC SYNDROME CHILDREN IN SOUTH INDIA

Arumugam

2017

Asian J Pharm Clin Res

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“…[14–17,31–35] All of the participants in these studies were children consisting of 928 patients with INS and 879 healthy controls; moreover, steroid resistance data were available for 724 patients comprising 488 patients with SS and 236 patients with SR, which were compared. The subjects in 4 studies were Asian [16,17,34,35] and those from the other 5 were Caucasian. [14,15,31–33] Seven studies reported genotype frequencies between patients with INS and healthy controls, [14–16,31,32,34,35] and 7 studies showed the genotype data of SS and SR groups.…”

Section: Resultsmentioning

confidence: 99%

“…However, these studies yielded inconsistent results. Youssef et al [14] reported that the T allele and TT genotype of rs1045642, and the T allele and GT, TT, and TT + AA genotypes of rs2032582 were significantly increased in patients with INS, but no significant evidence of association was found with any of these 3 SNPs in the cohort tested by Cizmarikova et al [15] Jafar et al [16] showed that the frequencies of homozygous mutant TT/AA genotypes of rs2032582 were significantly increased in affected children with steroid resistance, whereas Chiou et al [17] observed a trend with the T allele of rs1128503 in their cohort.…”

Section: Introductionmentioning

confidence: 99%

A PRISMA-compliant meta-analysis of MDR1 polymorphisms and idiopathic nephrotic syndrome

Han

Xu²,

Lü³

et al. 2017

Medicine

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“…While some studies reported higher expression levels in 2677TT/A subjects [26], others showed no differences between genotypes [27]. In our previous work, we had observed that homozygous mutant of SNP G2677T/A is prone to develop steroid-resistant nephrotic syndrome [24]. Another mechanism that may be responsible for persistent expression of P-gp could be due epigenetic influence; DNA methylation, histone acetylation, and micro-RNA activity.…”

Section: Discussionmentioning

confidence: 85%

Persistent expression and function of P-glycoprotein on peripheral blood lymphocytes identifies corticosteroid resistance in patients with systemic lupus erythematosus

et al. 2015

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Corticosteroids (CS) are the mainstay of treatment in systemic lupus erythematosus (SLE) patients. However, some patients have poor response to CS treatment. Among the multiple mechanisms of CS resistance, overexpression of P-glycoprotein (P-gp) on peripheral blood lymphocytes (PBL) may be one of them as this result in efflux of CS from lymphocytes. Thus, we evaluated the role of P-gp protein on PBLs in patients with SLE in its response to CS therapy. SLE patients (n = 42) (fulfilling ACR revised criteria) who were naïve to CS and immunosuppressive drugs were enrolled. Disease activity was assessed using SLE disease activity index (SLEDAI) and expression, and function of P-gp was evaluated by flow cytometry at baseline and after 3 months of therapy with CS. At 3 months, patients with SLEDAI >4 and SLEDAI ≤4 were grouped as nonresponders and responders, respectively. P-gp expression was significantly increased on PBLs of SLE patients as compared to healthy controls (p < 0.001). P-gp expression and function correlated with SLEDAI (r = 0.49, p = 0.005; and r = 0.49, p = 0.001, respectively). P-gp expression and function were not different in responders and nonresponders at baseline. However, at 3 months of CS therapy, P-gp expression and function decreased in responders (p < 0.001 and p < 0.005, respectively), whereas in nonresponders, it remained unchanged. Persistent overexpression and activity of P-gp are associated with poor response to CS in CS naïve patients of SLE.

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MDR-1 gene polymorphisms in steroid-responsive versus steroid-resistant nephrotic syndrome in children

Abstract: Patients with NS carrying homozygous mutants of single nucleotide polymorphism (SNP) G2677T/A are prone to develop SRNS. The synergistic effect of mutant genotypes of SNPs G2677T/A and C3435T in different combinations increase the risk of developing steroid resistance in patients with NS.

Cited by 42 publications

References 25 publications

IDENTIFICATION OF FUNCTIONAL SNPs OF MDR1 GENE AMONG NEPHROTIC SYNDROME CHILDREN IN SOUTH INDIA

IDENTIFICATION OF FUNCTIONAL SNPs OF MDR1 GENE AMONG NEPHROTIC SYNDROME CHILDREN IN SOUTH INDIA

A PRISMA-compliant meta-analysis of MDR1 polymorphisms and idiopathic nephrotic syndrome

Persistent expression and function of P-glycoprotein on peripheral blood lymphocytes identifies corticosteroid resistance in patients with systemic lupus erythematosus

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