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Involvement of Genetic Variation and Related Gene Expression Changes on Acute Rejection in Renal Transplant Recipients

H. Hwang1, J. Seo1, J. Kim1, Y. Kim1, J. Moon1, K. Jeong1, C. Kim2, J. Park3, B. Chung4, Y. Kim5, S. Lee1

1Division of Nephrology, Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul, Korea, Republic of, 2Division of Nephrology, Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Korea, Republic of, 3Department of Surgery, Samsung Medical Center, Seoul, Korea, Republic of, 4Division of Nephrology, Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea, Seoul, Korea, Republic of, 5Division of Nephrology, Department of Internal Medicine, College of Medicine, Inje University, Pusan, Korea, Republic of

Meeting: 2019 American Transplant Congress

Abstract number: A149

Keywords: Gene expression, Gene polymorphism, Genomic markers, Rejection

Session Information

Date: Saturday, June 1, 2019

Session Name: Poster Session A: Biomarkers, Immune Monitoring and Outcomes

Session Time: 5:30pm-7:30pm

 Presentation Time: 5:30pm-7:30pm

Location: Hall C & D

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*Purpose: Acute rejection (AR) is one of the major risk factors for renal allograft loss. The effect of genetic factors on the transplant outcomes has been clear. However, the correlation between genetic variation and acute rejection remains undetermined.

*Methods: We collected blood samples from recipients with biopsy-proven AR (n = 81) and with stable graft function (n = 48). Gene expression data was pooled from RNA microarray and RNA sequencing. Integrative analysis combining genome-wide association studies (GWAS) and expression quantitative trait loci (eQTL) was used to identify single nucleotide polymorphisms (SNPs) for acute rejection.

*Results: In eQTL analysis, we detected potential 35,465 SNPs, which correlated with RNA expression. We analyzed AR-related SNPs in GWAS with covariate adjustment, and detected 140 overlapped SNPs in integrative analyses of eQTL and GWAS. The corresponding genes of these SNPs were matched with genes whose expression level differs between patients with AR and stable graft, and three loci were finally mated. One locus is PFDN6, which involves the activation and development of lymphocyte. Two other loci encompass ZSCAN10 and HEBP2, which involves the DNA binding transcription factor activity and microtubule dynamics, respectively.

*Conclusions: Our integrated analysis of GWAS and eQTL helps to find relevant genes, which had both biological and clinical significance, and identify three novel acute rejection susceptibility loci in renal transplant recipients.

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To cite this abstract in AMA style:

Hwang H, Seo J, Kim J, Kim Y, Moon J, Jeong K, Kim C, Park J, Chung B, Kim Y, Lee S. Involvement of Genetic Variation and Related Gene Expression Changes on Acute Rejection in Renal Transplant Recipients [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/involvement-of-genetic-variation-and-related-gene-expression-changes-on-acute-rejection-in-renal-transplant-recipients/. Accessed January 23, 2021.

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