NPHS2 R229Q functional variant is associated with microalbuminuria in the general population

Pereira, Alexandre C.; Pereira, Aparecido B.; Mota, Glória F.; Cunha, Roberto S.; Herkenhoff, Fernando Luiz; Pollak, Martin R.; Mill, José Geraldo; Krieger, José Eduardo

doi:10.1111/j.1523-1755.2004.00479.x

Cited by 95 publications

(88 citation statements)

References 14 publications

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“…Furthermore, our results are in agreement with a previous report excluding linkage to diabetic ESRD for the NPHS2 and ACTN4 loci in White and African-American populations [8]. The only functional polymorphism studied here, R229Q in the NPHS2 gene, has been suggested to contribute to susceptibility to microalbuminuria in the general population [9]. However, we could not establish such a relationship between AER and the R229Q variant, or any other variant in the NPHS2 gene, in patients with type 1 diabetes.…”

Section: Discussionsupporting

confidence: 93%

Association analysis of podocyte slit diaphragm genes as candidates for diabetic nephropathy

et al. 2007

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Aims/hypothesis The slit diaphragm is an adhesion and signalling protein complex linking the interdigitating podocyte foot processes in the kidney glomerulus, and mutations in slit diaphragm-associated genes result in severe proteinuria. Here we report a genetic association analysis of four slit diaphragm genes, LRRC7, KIRREL, NPHS2 and ACTN4, in a Finnish diabetic nephropathy cohort. Materials and methods A total of 40 single nucleotide polymorphisms (SNPs) were genotyped in 1103 patients with type 1 diabetes. The patients were classified according to their renal status, and the genotype data were analysed in a cross-sectional case-control setting. To confirm positive associations, four SNPs were genotyped in 1,025 additional patients with type 1 diabetes. Results No associations with diabetic nephropathy were observed for any of the analysed SNPs. The SNPs were not associated with the time from the onset of diabetes to the diagnosis of nephropathy or with glomerular filtration rate or AER as quantitative variables. In a sex-specific sub-analysis, the variants rs979972 and rs749701 in the first intron of ACTN4 were nominally associated with diabetic nephropathy in females, with odds ratios of 1.81 (95% CI 1.18-2.79, p=0.007) and 1.93 (95% CI 1.26-2.96, p=0.003) respectively. Conclusions/interpretation Our study has not found any evidence that common variants in LRRC7, KIRREL, NPHS2 and ACTN4 contribute to susceptibility to diabetic nephropathy in Finnish patients with type 1 diabetes.

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Section: Discussionsupporting

confidence: 93%

Association analysis of podocyte slit diaphragm genes as candidates for diabetic nephropathy

et al. 2007

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“…This variant has a frequency of 4% in the general Cypriot population. It is worth mentioning that, although an earlier report had associated R229Q with microalbuminuria in the Brazilian population, a more recent work with larger numbers did not corroborate those data in a US adult population [13,14].…”

mentioning

confidence: 66%

Thin basement membrane nephropathy: is there genetic predisposition to more severe disease?

Deltas

2009

Pediatr Nephrol

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“…Its relevance is controversially discussed. In vitro studies demonstrated a reduced binding capacity to nephrin for R229Q-podocin (31), and some studies point to an association of R229Q and development of microalbuminuria in the general population (32) or an enhanced allele frequency of R229Q in nongenetic FSGS patients (31,33). Machuca et al reported a large number of FSGS patients heterozygous for R229Q in association with a second pathogenic mutation in NPHS2; these patients typically present with later onset of disease and slower progression to ESRD (34).…”

Section: Discussionmentioning

confidence: 99%

Immunosuppression and Renal Outcome in Congenital and Pediatric Steroid-Resistant Nephrotic Syndrome

Büscher

Kranz²,

Büscher³

et al. 2010

Clinical Journal of the American Society of Nephrology

170

119

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Background and objectives: Mutations in podocyte genes are associated with steroid-resistant nephrotic syndrome (SRNS), mostly affecting younger age groups. To date, it is unclear whether these patients benefit from intensified immunosuppression with cyclosporine A (CsA). The aim of this study was to evaluate the influence of podocyte gene defects in congenital nephrotic syndrome (CNS) and pediatric SRNS on the efficacy of CsA therapy and preservation of renal function.Design, settings, participants, & measurements: Genotyping was performed in 91 CNS/SRNS patients, irrespective of age at manifestation or response to CsA.Results: Mutations were identified in 52% of families (11 NPHS1, 17 NPHS2, 11 WT1, 1 LAMB2, 3 TRPC6). Sixty-eight percent of patients with nongenetic SRNS responded to CsA, most of them achieved complete remission. In contrast, none of the patients with genetic CNS/SRNS experienced a complete remission and only two (17%) achieved a partial response, both affected by a WT1 mutation. Preservation of renal function was significantly better in children with nongenetic disease after a mean follow-up time of 8.6 years (ESRD in 29% versus 71%).Conclusions: The mutation detection rate in our population was high (52%). Most patients with genetic CNS/SRNS did not benefit from CsA with significantly lower response rates compared with nongenetic patients and showed rapid progression to end-stage renal failure. These data strongly support the idea not to expose CNS/SRNS patients with inherited defects related to podocyte function to intensified immunosuppression with CsA.

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NPHS2 R229Q functional variant is associated with microalbuminuria in the general population

Abstract: These data have important implications for the understanding of microalbuminuria in the general population and may contribute to better ways of disease prediction and prevention.

Cited by 95 publications

References 14 publications

Association analysis of podocyte slit diaphragm genes as candidates for diabetic nephropathy

Association analysis of podocyte slit diaphragm genes as candidates for diabetic nephropathy

Thin basement membrane nephropathy: is there genetic predisposition to more severe disease?

Immunosuppression and Renal Outcome in Congenital and Pediatric Steroid-Resistant Nephrotic Syndrome

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