IDENTIFICATION OF NOVEL GENE BIOMARKERS ASSOCIATED WITH STEROID RESPONSIVENESS IN CHILDREN WITH NEPHROTIC SYNDROME

Abstract

Nephrotic Syndrome NS is a heterogeneous group of conditions with a multifactorial etiology Failure to respond to steroid treatment has an important ramification for the risk of developing progressive renal failure later in life Molecular studies performed in identifying mutations in NPHS1 NPHS2 candidate genes and ACE MDR1 as modifier genes involved in maintaining the structural integrity of the podocytes and renal pathophysiology functions Mutations in these genes are now being extensively studied to understand the association to steroid responsiveness in patients with NS Therefore it was thought that a systematic study within the context of a South Indian population could provide an understanding of the etiology of NS Towards this healthy subjects NS patients with and without resistance to steroid response were recruited and was screened for mutations by PCR Sanger sequencing NPHS1 showed 9 percent mutation frequency in SRNS patients all mutations and three single nucleotide polymorphism observed are novel In NPHS2 a mutational frequency of 18 percent was observed in SRNS patients of which 7 mutations are of novel findings Study on the associated pathway genes angiotensin converting enzyme and Multidrug Resistance Protein 1 gene polymorphism in NS did not show any significant difference between the three examined groups However interestingly the SNP G2677T A of MDR1 genotypes TT GT and GA showed a significant association in SRNS patients when compared with that of a SSNS and control group The importance of the mutations on the candidate genes and their association on the development of steroid resistance towards therapy in NS subjects are presented in the thesis newline