title: MDR1 haplotypes modify BEN disease risk: a study in Bulgarian patients with Balkan endemic nephropathy compared to healthy controls.
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.
authors.affiliation: Department of Medical Genetics, Medical University, Sofia, Bulgaria.
authors.forename: S
authors.initials: S
authors.lastname: Atanasova
authors.forename: N
authors.initials: N
authors.lastname: von Ahsen
authors.forename: T
authors.initials: T
authors.lastname: Dimitrov
authors.forename: V
authors.initials: V
authors.lastname: Armstrong
authors.forename: M
authors.initials: M
authors.lastname: Oellerich
authors.forename: D
authors.initials: D
authors.lastname: Toncheva
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D001449:Balkan Nephropathy / Q000453:epidemiology* / Q000235:genetics*; D002031:Bulgaria / Q000453:epidemiology; D016022:Case-Control Studies; D005260:Female; D019450:Genes, MDR / Q000235:genetics*; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011159:Population Surveillance; D017678:Sex Distribution
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1