FoxP3 유전자다형성과 신이식 성적의 연관성 분석

학위논문 (박사)-- 서울대학교 대학원 의과대학 의학과, 2017. 8. 송은영.Background. FoxP3 is the most reliable marker for regulatory T cells which play an important role in maintaining tolerance of renal allograft. Recently, FoxP3 gene polymorphisms have been reported to be associated with graft survival in renal transplantation. Methods. We analyzed the association of FoxP3 polymorphisms (rs3761548A/C, rs2280883C/T, rs5902434del/ATT, and rs2232365A/G) and graft outcome by polymerase chain reaction with sequence-specific primers (PCR-SSP) on 231 adult renal transplantation recipients performed during the period of 1996-2004 in Seoul National University Hospital. Results. Patients with rs2280883 TT genotype showed lower acute rejection rate compared to CC or CT genotype (26.9% vs 53.3%, P = 0.038). Patients with rs3761548 CC genotype showed better graft survival compared to AC or AA genotype (log rank test, P = 0.03). Patients with rs2280883 TT genotype showed better graft survival compared to CT or CC genotype (P = 0.02). Patients with rs3761548 CC genotype showed lower rate or recurrence of underlying glomerular disease compared to AC or AA genotype (P = 0.01). Conclusion. FoxP3 polymorphism rs3761548 CC and rs2280883 TT genotypes were associated with superior graft outcome of renal transplantation in Koreans. Further studies are needed in larger number of patients.Abstract ....................................................................................... i Contents ...................................................................................... iii List of tables................................................................................ v List of figures .......................................................................... vii List of abbreviations .............................................................. viii 1. Introduction ............................................................................ 1 2. Materials and Methods ......................................................... 4 2.1. Subjects ............................................................................ 4 2.2. Analysis of FoxP3 gene SNPs....................................... 5 2.3. Processing reference sequence data............................... 7 2.4. Predicting the effect of intron variant.......................... 8 2.5. Statistical analysis.......................................................... 9 3. Results ................................................................................... 11 3.1. Characteristics of the study population. .................... 11 3.2. Comparison of gene frequency with Korean population database............................................................................. 16 3.3. Linkage disequilibrium and haplotype-based association analysis ....................................................... 18 3.4. Association of FoxP3 polymorphisms with graft rejection ........................................................ 22 3.5. Graft survival and FoxP3 polymorphism................. 26 3.6. Recurrence of underlying glomerular disease posttransplant and FoxP3 polymorphism ...................................... 30 3.7. Posttransplant infection and FoxP3 polymorphism......................... 34 3.8. In-silico analysis of the intron variant on splicing efficiency of FoxP3 polymorphism........ 40 4. Discussion.............................................................................. 42 References ................................................................................. 47 Abstract in Korean .................................................................. 56Docto