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

Objective: This study was conducted to determine the frequency of C3435T and G2677T/C single nucleotide polymorphisms of multi drug resistancegene -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 intosteroid-resistant NS (SRNS) were 90 and steroid-sensitive NS (SSNS) were 83 and 198 blood samples were included as controls. All samples weresubjected to DNA extraction, and polymerase chain reaction followed by restriction fragment length polymorphism for identification of C3435T andG2677T/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% wereobserved. 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, earlieronset of NS as well as leads to steroid resistance. Whereas SNP G2677T/C gene polymorphisms do not have significant role observed in this studypopulation.Keywords: Nephrotic syndrome, Steroid-sensitive nephrotic syndrome, Steroid-resistant nephrotic syndrome, Multidrug resistance gene-1,Polymerase chain reaction followed by restriction fragment length polymorphism.