The amino acid mutations of the podocin in proteinuria: a meta-analysis

Abstract

(2015) The amino acid mutations of the podocin in proteinuria: a meta-analysis, Renal Failure, 37:8, 1329-1337 AbstractWhile many previous studies have reported an association between the single-nucleotide polymorphisms (SNPs) of the podocin and proteinuria occurred, a conclusive relationship has not been defined in every oligoallelic state of amino acid (AA) mutations in podocin. In this study, we performed a meta-analysis of the published data to investigate the impact of the oligoallelic AA mutations of the podocin on proteinuria; a total 16 AA mutations were investigated for oligoallelic pathogenicity. Despite significant heterogeneity within some of the comparisons, the results revealed significantly higher risks of proteinuria in early-onset (onset age 516) individuals for five mutations (P118L, R138Q, R168H, V180M, and V260E), and in all onset ages individuals for five mutations (R138Q, G140X, R229Q, V260E, and V290M) compared to non-variant individuals. We also tested the steroid response in individuals with R229Q and E237Q. No statistically significant differences in the two mutations carrier rate were observed between steroid resistance patients and controls. No AA mutation was selected for metaanalysis on the recurrence of proteinuria after renal transplantation as lack of control data. In conclusion, our meta-analysis tested the pathogenicity of the oligoallelic AA mutations in podocin and suggested the potential causative mutations, and the alleles showing an association with protein susceptibility. The sensitivity and specificity of each causative mutation are pending further testing.

NPHS2 gene sequencing results in children of the Azerbaijani population with different types of nephrotic syndrome caused by chronic glomerulonephritis

“…There is a contradiction in literature regarding this variant. While older studies showed this variant as being pathogenic (17,18) the new ones accept it as being benign (19)(20)(21)(22)(23). Despite the fact that there are several studies predicting c.59C>T to have a disease-causing effect in European, North American, Caucasian and South American populations (24), in our study, it was decided to classify it as VUS while further segregation and detailed pedigree analyses were planned.…”

“…Leu169Pro (21), Val180Met (25), Val290Met (21) and Arg-229Gln (21) were classifi ed as VUS because of insuffi cient evidences and lack of segregation analysis. Nevertheless, they are thought to be the cause of clinical manifestation in patients.…”