GENETICS OF NEPHROTIC SYNDROME IN SINGAPORE PAEDIATRICS PATIENTS

Abstract

The aims of this study are firstly to identify genetic variants in nephrin (NPHS1) and podocin (NPHS2), in paediatric patients with idiopathic NS in Singapore, secondly, to determine the presence of disease associations with these genetic variants, and lastly to investigate if there are any gene-gene interactions. NPHS1 c.294C>T, c.2289C>T and c.349G>A, as well as NPHS2, c.-51G>T were significantly associated with NS. c.288C>T was observed to have a protective effect, whereas c.-51G>T and c.1038A.G were associated with steroid-resistance. c.1038A>G was also associated with cyclosporine resistance. Composite genotypes of GG/CC/CT and GT/CC/CT for NPHS2 c.-51G>T and c.288C>T and NPHS1 c.2289C>T were significantly associated with NS. The composite genotypes of GG/CC/TT and GT/CC/CC were also associated with steroid resistance. We have shown a significant accumulation of rare variants in nephrotic patients compared to controls, and also in nephrotic patients with poor prognosis compared to those who responded well to therapy.