title: Polymorphisms of the MDR1 and MIF genes in children with nephrotic syndrome.
abstract: Oral steroid treatment is the first line of therapy for childhood nephrotic syndrome (NS). Nonetheless, some patients are resistant to this treatment. Many efforts have been made to explain the differences in the response to steroid treatment in patients with NS based on the genetic background. We have investigated single nucleotide polymorphisms of the MDR1 [C1236T (rs1128503), G2677T/A (rs2032582), and C3435T (rs1045642)] and MIF (G-173C, rs755622) genes in 170 children with NS. Of these children, 69 (40.6%) were initial steroid non-responders, and 23 (13.5% of total) developed chronic kidney disease. Renal biopsy findings, which were available for 101 patients, showed that 35 patients had minimal change lesion and 66 had focal segmental glomerulosclerosis. The frequencies of the MDR1 1236 CC (18.8 vs 7.2%) or TC (53.5 vs 43.5%) genotype and C allele (45.5 vs 29.0%) were significantly higher in the initial steroid responders than in the non-responders. Analysis of MDR1 three-marker haplotypes revealed that the frequency of the TGC haplotype was significantly lower in the initial steroid responders than in the non-responders (15.8 vs 29.0%). There was no association between the MIF G-173C polymorphism and clinical parameters, renal histological findings, and steroid responsiveness. These data suggest that the initial steroid response in children with NS may be influenced by genetic variations in the MDR1 gene.
authors.affiliation: Department of Pediatrics, Seoul National University Children's Hospital, 101 Daehang-no, Jongno-Gu, Seoul 110-744, Korea.
authors.forename: Hyun Jin
authors.initials: HJ
authors.lastname: Choi
authors.forename: Hee Yeon
authors.initials: HY
authors.lastname: Cho
authors.forename: Han
authors.initials: H
authors.lastname: Ro
authors.forename: So Hee
authors.initials: SH
authors.lastname: Lee
authors.forename: Kyung Hee
authors.initials: KH
authors.lastname: Han
authors.forename: Hyunkyung
authors.initials: H
authors.lastname: Lee
authors.forename: Hee Gyung
authors.initials: HG
authors.lastname: Kang
authors.forename: Il Soo
authors.initials: IS
authors.lastname: Ha
authors.forename: Yong
authors.initials: Y
authors.lastname: Choi
authors.forename: Hae Il
authors.initials: HI
authors.lastname: Cheong
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D005838:Genotype; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D019746:Intramolecular Oxidoreductases / Q000235:genetics*; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics*; D008297:Male; D009404:Nephrotic Syndrome / Q000188:drug therapy / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011239:Prednisolone / Q000627:therapeutic use
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005938:Glucocorticoids; D008263:Macrophage Migration-Inhibitory Factors; D011239:Prednisolone; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human