NPHS2 variation in sporadic focal segmental glomerulosclerosis

Louise M. McKenzie, Sher L. Hendrickson, William A. Briggs, Richard A. Dart, Stephen M. Korbet, Michele H. Mokrzycki, Paul L. Kimmel, Tejinder S. Ahuja, Jeffrey S. Berns, Eric E. Simon, Michael C. Smith, Howard Trachtman, Donna M. Michel, Jeffrey R. Schelling, Monique Cho, Yu C. Zhou, Elizabeth Binns-Roemer, Gregory D. Kirk, Jeffrey B. Kopp, Cheryl A. Winkler

Research output: Contribution to journalArticle

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Abstract

Mutations in NPHS2, the gene that encodes podocin, are well-established causes of both familial and sporadic steroid-resistant focal segmental glomerulosclerosis (FSGS) in the pediatric population, but have not been well-characterized in late-onset disease. To investigate the role of NPHS2 polymorphisms in sporadic cases of late-onset FSGS, we studied 377 biopsy-confirmed FSGS cases and 919 controls. We identified 18 single nucleotide polymorphisms (SNPs) by resequencing a subgroup of cases and controls, and subsequently genotyped African-American and European-American cases and controls for five missense SNPs, three SNPs within introns, and four SNPs in the 3′ untranslated region. No homozygotes or compound heterozygotes were observed for any missense mutation. R138Q carriers were more frequent among FSGS cases relative to controls (OR = 4.9, P = 0.06), but heterozygosity for the other four missense mutations was equally distributed among FSGS cases and controls. Finally, a common haplotype of noncoding SNPs carried by 20% of African-Americans, but not observed in European-Americans, was strongly associated with a 50% reduction in risk for sporadic FSGS (OR = 0.5, P = 0.001). These results indicate that genetic variation or mutation of NPHS2 may play a role in late-onset sporadic FSGS.

Original languageEnglish (US)
Pages (from-to)2987-2995
Number of pages9
JournalJournal of the American Society of Nephrology
Volume18
Issue number11
DOIs
StatePublished - Nov 2007

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Focal Segmental Glomerulosclerosis
Single Nucleotide Polymorphism
Missense Mutation
African Americans
Mutation
Homozygote
3' Untranslated Regions
Risk Reduction Behavior
Heterozygote
Introns
Haplotypes
Steroids
Pediatrics
Biopsy
Population
Genes

ASJC Scopus subject areas

  • Nephrology

Cite this

McKenzie, L. M., Hendrickson, S. L., Briggs, W. A., Dart, R. A., Korbet, S. M., Mokrzycki, M. H., ... Winkler, C. A. (2007). NPHS2 variation in sporadic focal segmental glomerulosclerosis. Journal of the American Society of Nephrology, 18(11), 2987-2995. https://doi.org/10.1681/ASN.2007030319

NPHS2 variation in sporadic focal segmental glomerulosclerosis. / McKenzie, Louise M.; Hendrickson, Sher L.; Briggs, William A.; Dart, Richard A.; Korbet, Stephen M.; Mokrzycki, Michele H.; Kimmel, Paul L.; Ahuja, Tejinder S.; Berns, Jeffrey S.; Simon, Eric E.; Smith, Michael C.; Trachtman, Howard; Michel, Donna M.; Schelling, Jeffrey R.; Cho, Monique; Zhou, Yu C.; Binns-Roemer, Elizabeth; Kirk, Gregory D.; Kopp, Jeffrey B.; Winkler, Cheryl A.

In: Journal of the American Society of Nephrology, Vol. 18, No. 11, 11.2007, p. 2987-2995.

Research output: Contribution to journalArticle

McKenzie, LM, Hendrickson, SL, Briggs, WA, Dart, RA, Korbet, SM, Mokrzycki, MH, Kimmel, PL, Ahuja, TS, Berns, JS, Simon, EE, Smith, MC, Trachtman, H, Michel, DM, Schelling, JR, Cho, M, Zhou, YC, Binns-Roemer, E, Kirk, GD, Kopp, JB & Winkler, CA 2007, 'NPHS2 variation in sporadic focal segmental glomerulosclerosis', Journal of the American Society of Nephrology, vol. 18, no. 11, pp. 2987-2995. https://doi.org/10.1681/ASN.2007030319
McKenzie, Louise M. ; Hendrickson, Sher L. ; Briggs, William A. ; Dart, Richard A. ; Korbet, Stephen M. ; Mokrzycki, Michele H. ; Kimmel, Paul L. ; Ahuja, Tejinder S. ; Berns, Jeffrey S. ; Simon, Eric E. ; Smith, Michael C. ; Trachtman, Howard ; Michel, Donna M. ; Schelling, Jeffrey R. ; Cho, Monique ; Zhou, Yu C. ; Binns-Roemer, Elizabeth ; Kirk, Gregory D. ; Kopp, Jeffrey B. ; Winkler, Cheryl A. / NPHS2 variation in sporadic focal segmental glomerulosclerosis. In: Journal of the American Society of Nephrology. 2007 ; Vol. 18, No. 11. pp. 2987-2995.
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