Polymorphism in the PBX1 gene is related to cystinuria in Brazilian families
| Autor: | Nayara I. Viana, Fabio Cesar Miranda Torricelli, Fabio C. Vicentini, Eduardo Mazzucchi, Ruan Pimenta, Miguel Srougi, Katia R. M. Leite, Ronaldo Morales Guimarães, Giovanni Scala Marchini, Alexandre Danilovic, Sabrina T. Reis, William C. Nahas |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult Male Heterozygote DNA Copy Number Variations Genotype Short Communication Short Communications SNP Single-nucleotide polymorphism Biology Nephrolithiasis Polymorphism Single Nucleotide Loss of heterozygosity 03 medical and health sciences 0302 clinical medicine hemic and lymphatic diseases medicine Humans Genetic Predisposition to Disease genetics Genotyping Alleles Genetic Association Studies Genetics cystine Cystinuria Homozygote Pre-B-Cell Leukemia Transcription Factor 1 Renal absorption Cell Biology medicine.disease SNP genotyping 030104 developmental biology 030220 oncology & carcinogenesis Molecular Medicine Female Brazil |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-4934 |
| Popis: | 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® 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. |
| Databáze: | OpenAIRE |
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