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Significant association between FOXP3 gene polymorphism and steroid-resistant acute rejection in living donor liver transplantation.

ABSTRACT: Previous studies have found that preferential accumulation of regulatory T (Treg) cells in liver allografts during acute cellular rejection (ACR) is associated with less severe rejection, suggesting a role of Treg cells in preventing excessive progress of ACR. We investigated the impact of single nucleotide polymorphisms (SNPs) in the Forkhead box P3 (FOXP3) gene, a master regulator gene of Treg cells, on ACR severity in liver transplant (LT) recipients. In total, 102 living donor LT patients were enrolled in this study and categorized into no rejection (n?=?86), steroid-sensitive acute rejection (SSAR; n?=?11), and steroid-resistant acute rejection (SRAR; n?=?5). FOXP3 SNPs -3499 A/G (rs3761547), -3279 A/C (rs3761548), and -924 A/G (rs2232365) were genotyped using the polymerase chain reaction restriction fragment length polymorphism technique. T-cell responses to allostimulation were evaluated by the mixed lymphocyte reaction assay. We found no statistical association between the FOXP3 SNP genotype frequencies and ACR incidence. However, significantly higher incidence of SRAR was observed in LT patients with the FOXP3 rs3761548 A/C+A/A genotype than in those with the C/C genotype (A/C+A/A versus C/C; no rejection, SSAR, SRAR, 85.71%, 0%, 14.29% versus 83.58%, 16.42%, 0%, respectively; P?=? 0.0005). The mixed lymphocyte reaction assay performed at the time of ACR diagnosis showed higher anti-donor CD4+ T-cell responses in patients carrying rs3761548 A/C+A/A than in those with the C/C genotype (P?=? 0.019). No significant association was observed between the incidence of SRAR and either rs3761547A/G or rs2232365 A/G. Infectious complications and overall survival were not related to FOXP3 SNPs. Conclusion: Our findings indicate that FOXP3 SNP rs3761548 A/C might be a predisposing factor for SRAR after liver transplantation. (Hepatology Communications 2017;1:406-420).

SUBMITTER: Verma S

PROVIDER: S-EPMC5721418 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Significant association between <i>FOXP3</i> gene polymorphism and steroid-resistant acute rejection in living donor liver transplantation.

Verma Sapana S Tanaka Yuka Y Shimizu Seiichi S Tanimine Naoki N Ohdan Hideki H

Hepatology communications 20170608 5

Previous studies have found that preferential accumulation of regulatory T (Treg) cells in liver allografts during acute cellular rejection (ACR) is associated with less severe rejection, suggesting a role of Treg cells in preventing excessive progress of ACR. We investigated the impact of single nucleotide polymorphisms (SNPs) in the Forkhead box P3 (<i>FOXP3</i>) gene, a master regulator gene of Treg cells, on ACR severity in liver transplant (LT) recipients. In total, 102 living donor LT pati ...[more]

PMID: 29404469

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Project description:Adult-to-adult living donors and recipients were studied to characterize patterns of liver growth and identify associated factors in a multicenter study. Three hundred and fifty donors and 353 recipients in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) receiving transplants between March 2003 and February 2010 were included. Potential predictors of 3-month liver volume included total and standard liver volumes (TLV and SLV), Model for End-Stage Liver Disease (MELD) score (in recipients), the remnant and graft size, remnant-to-donor and graft-to-recipient weight ratios (RDWR and GRWR), remnant/TLV, and graft/SLV. Among donors, 3-month absolute growth was 676 ± 251 g (mean ± SD), and percentage reconstitution was 80% ± 13%. Among recipients, GRWR was 1.3% ± 0.4% (8 < 0.8%). Graft weight was 60% ± 13% of SLV. Three-month absolute growth was 549 ± 267 g, and percentage reconstitution was 93% ± 18%. Predictors of greater 3-month liver volume included larger patient size (donors and recipients), larger graft volume (recipients), and larger TLV (donors). Donors with the smallest remnant/TLV ratios had larger than expected growth but also had higher postoperative bilirubin and international normalized ratio at 7 and 30 days. In a combined donor-recipient analysis, donors had smaller 3-month liver volumes than recipients adjusted for patient size, remnant or graft volume, and TLV or SLV (P = 0.004). Recipient graft failure in the first 90 days was predicted by poor graft function at day 7 (HR = 4.50, P = 0.001) but not by GRWR or graft fraction (P > 0.90 for each). Both donors and recipients had rapid yet incomplete restoration of tissue mass in the first 3 months, and this confirmed previous reports. Recipients achieved a greater percentage of expected total volume. Patient size and recipient graft volume significantly influenced 3-month volumes. Importantly, donor liver volume is a critical predictor of the rate of regeneration, and donor remnant fraction affects postresection function. Liver Transpl 21:79-88, 2015. © 2014 AASLD.

Dataset Information

Significant association between FOXP3 gene polymorphism and steroid-resistant acute rejection in living donor liver transplantation.

Publications

Significant association between <i>FOXP3</i> gene polymorphism and steroid-resistant acute rejection in living donor liver transplantation.

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