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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Polymorphism in the PBX1 gene is related to cystinuria in Brazilian families

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Reis, Sabrina T. [1, 2] ; Leite, Katia R. M. [1] ; Marchini, Giovanni S. [2] ; Guimaraes, Ronaldo M. [2] ; Viana, Nayara I. [1] ; Pimenta, Ruan C. A. [1] ; Torricelli, Fabio C. [2] ; Danilovic, Alexandre [2] ; Vicentini, Fabio Carvalho [2] ; Nahas, William Carlos [1] ; Srougi, Miguel [1] ; Mazzucchi, Eduardo [2]
Total Authors: 12
[1] Univ Sao Paulo, Sch Med, Lab Med Invest LIM55, Div Urol, Sao Paulo - Brazil
[2] Univ Sao Paulo, Sch Med, Endourol & Stone Dis Sect, Div Urol, Sao Paulo - Brazil
Total Affiliations: 2
Document type: Journal article
Source: JOURNAL OF CELLULAR AND MOLECULAR MEDICINE; v. 23, n. 2, p. 1593-1597, FEB 2019.
Web of Science Citations: 0

The aim of our study was to determine regions of loss of heterozygosity, copy number variation analysis, and single nucleotide polymorphisms (SNPs) in Brazilian patients with cystinuria. A linkage study was performed using DNA samples from six patients with cystinuria and six healthy individuals. Genotyping was done with the Genome-Wide Human SNP 6.0 arrays (Affymetrix, Inc., Santa Clara, CA, USA). For validation, SNPs were genotyped using a TaqMan (R) SNP Genotyping Assay Kit. The homozygote polymorphic genotype of SNP rs17383719 in the gene PBX1 was more frequent (P = 0.015) in cystinuric patients. The presence of the polymorphic allele for this SNP increased the chance of cystinuria by 3.0-fold (P = 0.036). Pre-B-cell leukaemia transcription factor 1 (PBX1) was overexpressed 3.3-fold in patients with cystinuria. However, when we compared the gene expression findings with the genotyping, patients with a polymorphic homozygote genotype had underexpression of PBX1, while patients with a heterozygote or wild-type homozygote genotype had overexpression of PBX1. There is a 3-fold increase in the risk of the development of cystinuria among individuals with this particular SNP in the PBX1 gene. We postulate that the presence of this SNP alters the expression of PBX1, thus affecting the renal absorption of cystine and other amino acids, predisposing to nephrolithiasis. (AU)

FAPESP's process: 13/17034-5 - Profile of genetic polymorphisms in patients with renal lithiasis and cystinuria
Grantee:Eduardo Mazzucchi
Support type: Regular Research Grants