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

Abstract

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.

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

“…(3435C>T), 3,23,24,26,[28][29][30][31][32][33] one study investigated two SNPs rs1128503 (1236C>T) and rs1045642 (3435C>T), 27 and one study evaluated only rs1045642 (3435C>T) 25 with SRNS.…”

“…Association of rs1128503 was assessed in a total of 424 patients from SRG and 866 patients from SSG, rs2032582 in 384 patients from SRG and 786 patients from SSG, and rs1045642 in 514 patients from SRG and 949 patients from SSG. From 12 studies, five studies were conducted in an Asian population, 3,25,[31][32][33] three were in a Caucasian population, 24,28,29 and the other four were in an African population. 23,26,27,30 For genotyping, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was applied in eight studies, 3,23,25,26,29,30,32,33 the TaqMan assay was used in two studies, 27,31 sequencings were conducted for one study, 28 and Mas-sARRAY was applied for one study.…”

“…From 12 studies, five studies were conducted in an Asian population, 3,25,[31][32][33] three were in a Caucasian population, 24,28,29 and the other four were in an African population. 23,26,27,30 For genotyping, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was applied in eight studies, 3,23,25,26,29,30,32,33 the TaqMan assay was used in two studies, 27,31 sequencings were conducted for one study, 28 and Mas-sARRAY was applied for one study. 24 From the HWE test for the control group among all included studies, one study showed deviation for rs1128503, 3 two studies showed deviation for rs2032582, 3,29 and three studies showed deviation for rs1045642.…”

“…24 From the HWE test for the control group among all included studies, one study showed deviation for rs1128503, 3 two studies showed deviation for rs2032582, 3,29 and three studies showed deviation for rs1045642. 3,25,27 Evaluation of the NOS scoring system for all included studies showed that most of the studies belong to high-quality score range, except one study in the medium score range depicted in Table 1.…”

“…Other studies examining the correlation of ABCB1 polymorphisms with SRNS also resulted in conflicting outcomes. [25][26][27][28][29][30][31][32][33] Based on the unconvincing outcomes of the previous casecontrol studies in different ethnicities, we carried out a comprehensive systemic updated meta-analysis to validate the association of ABCB1 rs1128503, rs2032582, and rs1045642 gene polymorphisms with SRNS. Meanwhile, we aimed to provide a better understanding of the correlation of ABCB1 polymorphisms and SRNS in steroid receiving patients.…”