Department of Pediatrics, Seoul National University Children's Hospital, 101 Daehang-no, Jongno-Gu, Seoul 110-744, Korea.
Pediatr Nephrol. 2011 Nov;26(11):1981-8. doi: 10.1007/s00467-011-1903-0. Epub 2011 May 8.
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.
口服类固醇治疗是儿童肾病综合征（NS）的一线治疗方法。然而，有些患者对此治疗方法有抗性。许多人致力于从遗传背景的角度来解释 NS 患者对类固醇治疗反应的差异。我们研究了 170 名 NS 儿童中 MDR1 [C1236T（rs1128503）、G2677T/A（rs2032582）和 C3435T（rs1045642）]和 MIF（G-173C，rs755622）基因的单核苷酸多态性。在这些儿童中，有 69 名（40.6%）是初始类固醇无反应者，有 23 名（占总数的 13.5%）发展为慢性肾脏病。对于 101 名患者的肾脏活检结果显示，35 名患者存在微小病变，66 名患者存在局灶节段性肾小球硬化。在初始类固醇反应者中，MDR1 1236 CC（18.8%比 7.2%）或 TC（53.5%比 43.5%）基因型和 C 等位基因（45.5%比 29.0%）的频率明显高于非反应者。对 MDR1 三标记单倍型的分析表明，初始类固醇反应者中 TGC 单倍型的频率明显低于非反应者（15.8%比 29.0%）。MIF G-173C 多态性与临床参数、肾脏组织学发现和类固醇反应性之间没有关联。这些数据表明，NS 儿童的初始类固醇反应可能受 MDR1 基因的遗传变异影响。
