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Polymorphism in the PBX 1 gene is related to cystinuria in Brazilian families

2018; Wiley; Volume: 23; Issue: 2 Linguagem: Inglês

10.1111/jcmm.13981

1582-4934

Sabrina T. Reis, Kátia Ramos Moreira Leite, Giovanni Scala Marchini, Ronaldo M. Guimarães, Nayara Izabel Viana, Ruan Pimenta, Fábio César Miranda Torricelli, Alexandre Danilovic, Fábio C. Vicentini, William Carlos Nahas, Miguel Srougi, Eduardo Mazzucchi,

Amino Acid Enzymes and Metabolism

Abstract The aim of our study was to determine regions of loss of heterozygosity, copy number variation analysis, and single nucleotide polymorphisms ( SNP s) 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, SNP s were genotyped using a TaqMan ® SNP Genotyping Assay Kit. The homozygote polymorphic genotype of SNP rs17383719 in the gene PBX 1 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 ( PBX 1) 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 PBX 1, while patients with a heterozygote or wild‐type homozygote genotype had overexpression of PBX 1. There is a 3‐fold increase in the risk of the development of cystinuria among individuals with this particular SNP in the PBX 1 gene. We postulate that the presence of this SNP alters the expression of PBX 1, thus affecting the renal absorption of cystine and other amino acids, predisposing to nephrolithiasis.