Polymorphism in the PBX1 gene is related to cystinuria in Brazilian families
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Citações na Scopus
2
Tipo de produção
article
Data de publicação
2019
Título da Revista
ISSN da Revista
Título do Volume
Editora
WILEY
Citação
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, v.23, n.2, p.1593-1597, 2019
Resumo
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.
Palavras-chave
cystine, genetics, SNP
Referências
- Alkan C, 2011, NAT REV GENET, V12, P363, DOI 10.1038/nrg2958
- Bhuwania R, 2012, J CELL SCI, V125, P2300, DOI 10.1242/jcs.100032
- Chillaron J, 2010, NAT REV NEPHROL, V6, P424, DOI 10.1038/nrneph.2010.69
- Dello Strologo L, 2002, J AM SOC NEPHROL, V13, P2547, DOI 10.1097/01.ASN.0000029586.17680.E5
- Eggermann T, 2012, ORPHANET J RARE DIS, V7, DOI 10.1186/1750-1172-7-19
- Fang ZY, 2013, J BIOL CHEM, V288, P7918, DOI 10.1074/jbc.M112.416842
- Fazaeli S, 2017, IRAN J KIDNEY DIS, V11, P138
- Gibbs RA, 2003, NATURE, V426, P789, DOI 10.1038/nature02168
- He Lei, 2009, Human Genomics, V3, P195
- Koulivand L, 2015, UROLITHIASIS, V43, P447, DOI 10.1007/s00240-015-0794-0
- Leclerc D, 2002, KIDNEY INT, V62, P1550, DOI 10.1046/j.1523-1755.2002.00602.x
- Mahdavi M, 2018, MOL BIOL REP, V45, P1165, DOI 10.1007/s11033-018-4269-6
- Markazi S, 2016, IRAN J KIDNEY DIS, V10, P44
- Sachidanandam R, 2001, NATURE, V409, P928, DOI 10.1038/35057149
- Schnabel CA, 2003, GENESIS, V37, P123, DOI 10.1002/gene.10235