Significance of Gene Polymorphism on Infectious Complications and Rejection after Liver Transplantation

H. Egawa¹, T. Kato¹, Y. Kotera¹, A. Ohmori¹, G. Shibuya¹, S. Yamashita¹, S. Ariizumi¹, M. Yamamoto¹, T. Ishizuka², Y. Tanaka³, H. Ohdan³

¹Tokyo Women's Medical University, Tokyo, Japan, ²Clinical Labotratory, Tokyo Women's Medical University, Tokyo, Japan, ³Surgery, Hiroshima University, Hiroshima, Japan

Meeting: 2020 American Transplant Congress

Abstract number: A-299

Keywords: Infection, Liver transplantation, Polymorphism, Rejection

Session Information

Session Name: Poster Session A: Biomarkers, Immune Assessment and Clinical Outcomes

Session Type: Poster Session

Date: Saturday, May 30, 2020

Session Time: 3:15pm-4:00pm

Presentation Time: 3:30pm-4:00pm

Location: Virtual

*Purpose: Clinical application of gene polymorphism is a key of precision medicine in the field of organ transplantation. Infection and rejection are major factors affecting outcomes. Hiroshima group has reported significance of Fc-gamma receptor (Fc-rR) polymorphism in infectious complications and FOXP3 gene polymorphism in steroid resisted acute rejection after liver transplantation (Am J Transplant. 2016;16:625-33, Hepatology Communication 2017;1:406-420). We investigated impacts of gene polymorphism of Fc-rR2A(131H/R) and Fc-rR3A(158 F/V), and FOXP3 (rs3761548) in our liver transplant cohort in which surgical factors and immunosuppression regimens were varied from the original institution.

*Methods: Ninety patients underwent liver transplantation (LT) consisting of 11 deceased donor LT and 79 living donor LT. Among them 59 patients of whom both of written informed consent and preserved pretransplant DNA were available were enrolled. Clinical data of treated ACR, steroid resistant ACR, positive CMV antigenemia, CMV diseases requiring treatment, blood stream infection (BSI) of any kind of bacteria, gram positive coccus BSI, BSI accompanied with bacteria other than streptococcus epidermidis, and survival were collected. The relationship between the 3 polymorphism and these factors were analyzed with JMP pro 14.0.0..

*Results: Variation of genotypes were HH/RH/RR: 36/23/0 in Fc-rR2A, FF/VF/VV: 33/21/5 in Fc-rR3A, and AA/AC/CC: 9/4/46 in FOXP3, respectively. Genotype HH of Fc-rR2A was significantly associated with incidence of positive CMV antigenemia (p=0.003), CMV diseases (p=0.015), and BSI accompanied with bacteria other than streptococcus epidermidis (p=0.048). Genotypes of Fc-rR3A had no significant association. Genotype AC of FOXP3 was associated with steroid resistant ACR (p=0.001). Log-rank analysis showed ACR, steroid resistant ACR, BSI, gram positive coccus BSI, intra-abdominal infection requiring laparotomy, and genotype AC of FOXP3 were significant risks for mortality.

*Conclusions: Although this is a preliminary study with a small cohort, it was confirmed that genotypes of Fc-rR2A and FOXP3 were significantly associated with postoperative infection and steroid resistant rejection, respectively. Gene polymorphism could have a potential to contribute to organ transplantation as precision medicine. A large scale multicenter study is running currently under a fund of Japan Agency for Medical Research and Development.

To cite this abstract in AMA style:

Egawa H, Kato T, Kotera Y, Ohmori A, Shibuya G, Yamashita S, Ariizumi S, Yamamoto M, Ishizuka T, Tanaka Y, Ohdan H. Significance of Gene Polymorphism on Infectious Complications and Rejection after Liver Transplantation [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/significance-of-gene-polymorphism-on-infectious-complications-and-rejection-after-liver-transplantation/. Accessed December 1, 2023.

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