Login to Access Video or Poster Abstract: MP12-10
Sources of Funding: FAPESP 2013/17034-5

Introduction

Cystinuria is a recessive disorder characterized by impaired tubular reabsorption of cystine and dibasic amino acids. Some studies in the literature have shown mutations in the SLC3A1 gene associated with type A cystinuria that follows a complete recessive inheritance in half of the cases. The other half has been related to mutations in the SLC7A9 gene considered responsible for cystinuria type B presumably inherited by an incomplete dominant manner. Considering the paucity of studies on the genetic basis of cystinuria, we performed genome-wide human SNP array, aiming to find some single nucleotide polymorphisms (SNPs) related to cystinuria development. To confirm the microarray results we performed PCR (Polymerase Chain Reaction) searching for five SNPs that we found related to the disease and two others reported in the literature.

Methods

DNA samples from peripheral white blood cells were extracted from eight patients with cystinuria and 10 healthy subjects with no renal calculi that composed the control group. The SNPs were genotyped using a TaqMan® SNP Genotyping Assay Kit.

Results

The homozygote polymorphic genotype of SNP rs17383719 in gene PBX1 was significantly more frequent among cystinuric patients (p=0.015). The occurrence of the polymorphic allele for this SNP was associated with a 3-fold increased risk of cystinuria (p=0.036). The polymorphic alleles of SNPs rs913034 and rs7096453 (SVIL) were more frequent in the control group (p=0.04 and p=0.08, respectively). We did not detect polymorphic homozygote genotype in the SNPs for SLC7A9 (rs140134166) and SLC3A1 (rs200248046) genes.

Conclusions

This is the first study describing genetic variations in patients with cystinuria. The most important finding was the 3-fold increased risk for the development of the disease for the SNP in the PBX1 gene. PBX1 (Pre-B-cell-leukemia transcription factor 1) is a member of a transcription factors family associated with kidney development, but there are no studies in the literature associating this gene with nephrolithiasis. We postulate that the presence of SNP may change the gene expression of PBX1 affecting the renal absorption of cystine and other amino acids predisposing to nephrolithiasis.

Funding

FAPESP 2013/17034-5