The podocin V260E mutation predicts steroid resistant nephrotic syndrome in black South African children with focal segmental glomerulosclerosis

Melanie A Govender,Cecil Levy,Glenda Moonsamy,Michèle Ramsay,Errol Gottlich,Cheryl A Winkler,June Fabian,Heather Maher

doi:10.1038/s42003-019-0658-1

Abstract

In black African children with focal segmental glomerulosclerosis (FSGS) there are high rates of steroid resistance. The aim was to determine genetic associations with apolipoprotein L1 (APOL1) renal risk variants and podocin (NPHS2) variants in 30 unrelated black South African children with FSGS. Three APOL1 variants were genotyped and the exons of the NPHS2 gene sequenced in the cases and controls. APOL1 risk alleles show a modest association with steroid sensitive nephrotic syndrome (SSNS) and steroid resistant nephrotic syndrome (SRNS). The NPHS2 V260E variant was present in SRNS cases (V/V = 5; V/E = 4; E/E = 11), and was absent in SSNS cases. Haplotype analysis suggests a single mutation origin for V260E and it was associated with a decline in kidney function over a 60-month period (p = 0.026). The V260E variant is a good predictor of autosomal recessive SRNS in black South African children and could provide useful information in a clinical setting.

Highlights

In black African children with focal segmental glomerulosclerosis (FSGS) there are high rates of steroid resistance
Genetic counselling services are available, but limited, and our goal is to develop an affordable assay with a high predictive value to detect children with kidney disease who are unlikely to respond to steroid treatment
Our study identified a common African NPHS2 V260E variant associated with steroid resistant FSGS in black South African children

Summary

Introduction

In black African children with focal segmental glomerulosclerosis (FSGS) there are high rates of steroid resistance. The aim was to determine genetic associations with apolipoprotein L1 (APOL1) renal risk variants and podocin (NPHS2) variants in 30 unrelated black South African children with FSGS. Three coding variants in the apolipoprotein L1 (APOL1) gene are significantly associated with susceptibility to FSGS and a spectrum of chronic kidney disease (CKD) in African Americans[15,16]. These variants include two non-synonymous variants collectively referred to as the G1 risk allele (rs73885319 and rs60910145) and a 6 bp in-frame deletion (rs71785313) referred to as the G2 risk allele[16,17].

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