한국인 신이식 수혜자에서 transforming growth factor-β1 및 vascular endothelial growth factor 유전자의 단일염기다형성이 만성 이식신 신병증과 이식신 생존율에 미치는 영향 = Association of Transforming Growth Factor-β1 and Vascular Endothelial Growth Factor Gene Polymorphisms with Chronic Allograft Nephropathy and Graft Survival in Korean Renal Transplant Recipients

국문 초록 (Abstract)

목적: 염증반응과 섬유화에 관여하는 Transforming growth factor-β1 (TGF-β1)와 이식신에 대한 cytoprotection에 관여하는 vascular endothelial growth factor (VEGF)는 만성 이식신 신병증 (CAN)의 발생과 연관이 있을 것으로 추측되어 왔다. 이에 저자들은 한국인 신이식 수혜자를 대상으로 TGF-β1 및 VEGF 유전자 SNP과 이식신 생존율 및 CAN과의 상관관계에 대해 조사하였다. 방법: 경북대학교병원에서 신이식을 시행한 환자 중 유전자 분석에 동의한 221명과 건강한 대조군 148명을 대상으로 TGF-β1 유전자의 C-509T 및 T869C, VEGF 유전자에 있는 C-2578A, C405G의 유전자형을 분석하였다. 신이식 후 CAN이나 만성 calcineurin inhibitor 신독성으로 진단된 경우를 신병증군 (n=21)으로 그렇지 않은 경우를 정상 이식군 (n=200)으로 분류하였다. 결과: 신이식 환자군과 정상 대조군에서 확인된 TGF-β1 (C-509T, T869C) 및 VEGF 유전자의 SNP (C- 2578A, C405G)의 유전자형의 빈도는 Hardy-Weinberg 평형에 따른 기대빈도와 유의한 차이가 없었고, 신이식 환자군과 정상 대조군에 있어 TGF-β1 및 VEGF 유전자 SNP의 유전자형과 대립형질의 빈도에는 유의한 차이가 없었다. TGF-β1의 C-509T와 T869C 및 VEGF의 C-2578A와 C405G는 강한 유전적 상관 관계를 보였고 (D`=0.78-0.98), 두 군 간 각각의 일배체형 간의 빈도 차이는 없었다. 전체 신이식 환자를 대상으로 TGF-β1 및 VEGF 유전자 SNP의 유전자형에 따라 두 군으로 나누어 Kaplan-Meier 생존분석을 시행한 결과 이식신 생존율은 유의한 차이가 없었고, 저농도 혹은 고농도의 cytokine 생산과 관련된 유전자형에 따른 이식신 생존율도 각 cytokine 모두 유사하였다. 결론: 본 연구에서 조사한 TGF-β1 및 VEGF 유전자 SNP은 한국인 신이식 수혜자에서 이식신 생존 또는 만성 이식신 신병증 발생 여부에 따라 차이를 보이지 않았다.

다국어 초록 (Multilingual Abstract)

Purpose: Transforming growth factor-β1 (TGF-β1) has been associated with the promotion of renal allograft interstitial fibrosis and thereby chronic allograft nephropathy (CAN). Vascular endothelial growth factor (VEGF) has been shown to contribute to cytoprotection of the graft after kidney transplantation. We investigated the influence of single nucleotide polymorphisms (SNPs) of the TGF-β1 (C-509T and T869C) and the VEGF gene (C-2578A and C405G) on graft survival and the development of CAN. Methods: Genotyping was carried out using a real-time polymerase chain reaction which was performed on the LightCycler480 in 221 Korean renal transplant recipients and 148 healthy controls. According to the presence of CAN or chronic calcineurin inhibitor nephrotoxicity, the recipients were separated into the CAN (n=21) and the No CAN (n=200) groups. Results: The genotype frequencies of the SNPs were in Hardy-Weinberg equilibrium. The distributions of genotypes and alleles did not differ between recipients and controls. No significant differences were observed in the genotype distributions and allele frequencies between the CAN and the No CAN groups. The frequencies of haplotypes were not significantly different between the two groups, either. There were no statistically significant effects of TGF-β1 and VEGF gene polymorphisms on graft survival. Conclusion: This study did not show any statistically significant effects of four selected SNPs of the TGF-β1 and the VEGF genes on the development of CAN and graft survival in Korean renal transplant recipients.

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