Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
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Polymorphisms of the NR3C1 gene in Korean children with nephrotic syndrome

한국 신증후군 환아에서 NR3C1 유전자 다형성 분석

  • Cho, Hee Yeon (Department of Pediatrics, Seoul National University Children's Hospital) ;
  • Choi, Hyun Jin (Department of Pediatrics, Seoul National University Children's Hospital) ;
  • Lee, So Hee (Department of Pediatrics, Seoul National University Children's Hospital) ;
  • Lee, Hyun Kyung (Department of Pediatrics, Seoul National University Children's Hospital) ;
  • Kang, Hee Kyung (Kidney Research Institute, Medical Research Center, Seoul National University College of Medicine, Research Center for Rare Diseases) ;
  • Ha, Il Soo (Kidney Research Institute, Medical Research Center, Seoul National University College of Medicine) ;
  • Choi, Yong (Kidney Research Institute, Medical Research Center, Seoul National University College of Medicine) ;
  • Cheong, Hae Il (Kidney Research Institute, Medical Research Center, Seoul National University College of Medicine, Research Center for Rare Diseases)
  • 조희연 (서울대학교 어린이병원 소아과학교실) ;
  • 최현진 (서울대학교 어린이병원 소아과학교실) ;
  • 이소희 (서울대학교 어린이병원 소아과학교실) ;
  • 이현경 (서울대학교 어린이병원 소아과학교실) ;
  • 강희경 (서울대학교 의과대학 신장연구소, 희귀병 연구소) ;
  • 하일수 (서울대학교 의과대학 신장연구소) ;
  • 최용 (서울대학교 의과대학 신장연구소) ;
  • 정해일 (서울대학교 의과대학 신장연구소, 희귀병 연구소)
  • Received : 2009.07.02
  • Accepted : 2009.09.18
  • Published : 2009.11.15
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Abstract

Purpose : Idiopathic nephrotic syndrome (NS) can be clinically classified as steroid-sensitive and steroid-resistant. The detailed mechanism of glucocorticoid action in NS is currently unknown. Methods : In this study, we investigated 3 known single nucleotide polymorphisms (SNPs) (ER22/23EK, N363S, and BclI) of the glucocorticoid receptor gene (the NR3C1 gene) in 190 children with NS using polymerase chain reaction-restriction fragment length polymorphism and analyzed the correlation between the genotypes and clinicopathologic features of the patients. Results : Eighty patients (42.1%) were initial steroid nonresponders, of which 31 (16.3% of the total) developed end-stage renal disease during follow-up. Renal biopsy findings of 133 patients were available, of which 36 (31.9%) showed minimal changes in NS and 77 (68.1%) had focal segmental glomerulosclerosis. The distribution of the BclI genotypes was comparable between the patient and control groups, and the G allele frequencies in both the groups were almost the same. The ER22/23EK and N363S genotypes were homogenous as ER/ER and NN, respectively, in all the patients and in 100 control subjects. The BclI genotype showed no correlation with the NS onset age, initial steroid responsiveness, renal pathologic findings, or progression to end-stage renal disease. Conclusion : These data suggested that the ER22/23EK, N363S, and BclI SNPs in the NR3C1 gene do not affect the development of NS, initial steroid responsiveness, renal pathologic lesion, and progression to end-stage renal disease in Korean children with NS.

목 적 : 특발성 신증후군은 소아의 가장 흔한 일차성 사구체 질환 중의 하나이다. 신증후군은 초기 경구 스테로이드 치료에 대한 반응에 따라서 임상적으로 스테로이드 반응성 신증후군과 스테로이드 저항성 신증후군으로 분류될 수 있다. 그러나 현재까지 신증후군에서 스테로이드의 정확한 작용 기전은 알려져 있지 않다. 신증후군 환자를 대상으로 여러 가지 유전자 다형성을 분석함으로써 스테로이드 치료에 대한 반응의 차이를 설명하려는 여러 시도들이 있어왔다. 방 법 : 본 연구에서는 190명의 신증후군 환자를 대상으로 NR3C1 유전자 다형성(ER22/23EK, N363S, BclI)을 확인하여 유전형과 임상-병리 양상의 연관성에 대해서 분석하였다. 결 과 : 신증후군 환자의 평균 연령은 4.95세였고 남아가 134명이었다. 11명의 환자는 신증후군의 가족력이 있었다. 그러나 이 환자들을 대상으로 NPHS2, WT1, ACTN4, TRPC6 유전자 분석을 시행한 결과 이상 소견은 발견되지 않았다. 80명의 환자(42.1%)는 초기 스테로이드 저항성이었고 그 중 31명의 환자는 말기 신질환으로 진행하였다. 신장 조직 검사는 113명의 환자를 대상으로 시행되었고 그 중 36명의 환자(31.9%)는 미세변화 신증후군이었고 77명의 환자(68.1%)는 초점성 분절성 사구체 경화증이었다. BclI 유전형을 비교하였을 때 G allele 빈도는 환자군과 대조군에서 차이가 없었다. ER22/23EK과 N363S 유전형은 각각 ER/ER과 NN으로 환자군과 대조군에서 동일한 양상을 보였다. BclI 유전형은 신증후군의 발병 나이, 초기 스테로이드 반응 여부, 신장의 병리학적 소견, 말기 신질환으로의 진행여부와 연관성을 보이지 않았다. 결 론 : 한국 신증후군 환아를 대상으로 한 이 연구 결과는 NR3C1 유전자의 ER22/23EK, N363S 및 BclI 유전자 다형성이 신증후군의 발병, 초기 스테로이드 치료에 대한 반응, 신장의 조직학적 소견 및 신 기능의 저하에 영향을 미치지 않음을 보여준다.

Keywords

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