Martina Cizmarikova, Ludmila Podracka, Lucia Klimcakova, Viera Habalova, Andrej Boor, Jan Mojzis, Ladislav Mirossay
Department of Pharmacology , P.J. Safarik University, Faculty of Medicine, Kosice, Slovakia
Med Sci Monit 2015; 21:59-68
The role of the multidrug resistance-1 (MDR1 or ABCB1) gene polymorphisms 1236T>C, 2677T>G, and 3435T>C was studied in relation to susceptibility, demographics, and pathological characteristics, as well as their role in the therapeutic response (TR) to prednisone treatment in children with idiopathic nephrotic syndrome (INS).
Material and Methods: The polymorphisms were analyzed using the polymerase chain reaction-restriction fragment length polymorphism method in 46 children with INS and in 100 healthy controls. Different genetic models (codominant, dominant, recessive, and overdominant) were used for testing of associations between polymorphisms and phenotypes.
Results: Statistical analysis showed a significantly increased chance of TR in children carrying 3435TC genotype (OR=5.13, 95% CI=1.18–22.25; overdominant model). Moreover, INS patients under 6 years of age had significantly decreased frequencies of MDR1 1236CC (7.7% vs. 35%, p=0.029) or 2677GG (3.8% vs. 30.0%, p=0.033) genotypes. We also observed that patients with minimal change in disease and patients under 6 years of age at the onset of INS were initial responders more frequently when compared with children with focal segmental glomerulosclerosis and patients ≥6 years old at the onset (p=0.0001, p=0.027, respectively).
Conclusions: These data suggest that prednisone TR may be influenced by histology, age at the onset of INS, and MDR1 3435T>C polymorphism. The MDR1 1236T>C and 2677T>G polymorphisms were significantly associated with age at onset. Larger multicenter studies and studies across other ethnic groups are needed to elucidate the contradictory implications of MDR1 polymorphisms with INS in children.
Keywords: Child, Alleles, Gene Frequency, Genotype, Glomerulosclerosis, Focal Segmental - genetics, Haplotypes, Nephrotic Syndrome - genetics, P-Glycoproteins - genetics, Pharmacogenetics, Polymerase Chain Reaction, Polymorphism, Genetic, Prednisone - therapeutic use, Remission Induction, Slovakia, Steroids - therapeutic use