b51de786-9344-4b07-8ad7-4890e41ff115
title
MDR1  haplotypes modify BEN disease risk: a study in Bulgarian patients with Balkan endemic nephropathy compared to healthy controls.
c38710f9-6aaf-4d45-9a9e-a59a7b40ce55
abstract
BACKGROUND: Balkan endemic nephropathy (BEN) is a slow progressive nephropathy with frequent occurrence of uroepithelial tumors in the upper urinary tract. Genetic factors involved in xenobiotic detoxification mechanisms may cause genetic predisposition to BEN and influence the risk for this disease. Polymorphic  MDR1  variants with decreased  P-glycoprotein (P-gp)  activity modulate the risk for renal neoplasm. We have therefore investigated the impact of  MDR1  polymorphisms on BEN manifestation. METHODS: The constitutional genotype frequencies of two SNPs ( C3435T  and  G2677T ) in the  MDR1  gene in 112 healthy control subjects were investigated and compared with those of 96 patients with BEN. Identification of the SNPs was done with rapid cycle real-time PCR and melting curve analysis with allele-specific probes. RESULTS: The frequency of mutant alleles was comparable in both groups. Significant differences were revealed when the  MDR1  haplotypes were analyzed. Individuals with a predicted haplotype 12 (2677G/3435T) were less frequent in BEN cases (frequency 7.3%) than in controls (16.1%, p = 0.006). We found that carriers of the haplotype 12 had a decreased risk for BEN (OR = 0.411; 0.21-0.78). CONCLUSIONS: The data suggest that haplotype 12 is protective against BEN. There is no clear molecular explanation of the  MDR1  haplotype effects on the protein activity, which can explain the modified effect of the haplotype 12 on BEN risk.