Validation of Single Nucleotide Polymorphisms for Acute Renal Graft Rejection

H. Hwang¹, J. Kong¹, J. Kim¹, Y. Kim¹, J. Moon¹, K. Jeong¹, J. Park², J. Park³, T. Ban⁴, J. Yang⁵, C. Ahn⁶, S. Lee¹

¹Division of Nephrology, Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul, Korea, Republic of, ²Konkuk University School of Medicine, Seoul, Korea, Republic of, ³Yeungnam University Hospital, Seoul, Korea, Republic of, ⁴Eunpyeong St. Mary's Hospital The Catholic University of Korea, College of Medicine, Seoul, Korea, Republic of, ⁵Department of Surgery, Seoul National University Hospital, Seoul, Korea, Republic of, ⁶Division of Nephrology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea, Republic of

Meeting: 2020 American Transplant Congress

Abstract number: D-061

Keywords: Genomic markers, Kidney transplantation

Session Information

Session Name: Poster Session D: Kidney: Acute Cellular Rejection

Session Type: Poster Session

Date: Saturday, May 30, 2020

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

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

Location: Virtual

*Purpose: Genome-wide association studies (GWAS) has identified potential single nucleotide polymorphisms (SNPs), which is associated with acute rejection in renal transplant recipients. We sought to validate the association between acute rejection and potential SNPs identified in previous GWAS.

*Methods: We genotyped 278 renal transplants recipients with acute rejection and 1101 control patients from KOTRY database using Taqman assays. Five SNPs within four genes were analyzed to investigate the association with biopsy-proven acute T cell-mediated rejection and treated-borderline changes occurring in the first year after transplantation.

*Results: Of five SNPs, rs7976329 (PTPRO) and rs10765602 (CCDC67) showed significantly lower minor allele frequency in patients with acute rejection (P = 0.009 and P = 0.046, respectively). rs2942857 (UGT2B10) and rs294768 (7.9 kb 5’ of UGT2B10) are in strong linkage disequilibrium (r² = 0.99) and they were not associated with risk of acute rejection. rs146480420 did not show any genotypic variants in this cohort. CC genotype in rs7976329 decreased risk of acute rejection after adjustment for multiple variables (odds ratio [OR] 0.43, 95% confidence interval [CI] 0.21-0.89; P = 0.024) compared to TT genotype. In recessive inheritance model, CC genotype was also associated with lower risk of AR (OR 0.45, 95% CI 0.22-0.94; P = 0.020), which is opposite to findings of previous GWAS. rs10765602 did not significant association with AR in multivariate model.

*Conclusions: In this large cohort study, we could not replicate the significant findings from recent GWAS. Our results emphasize the importance of validation findings and call for large collaborative research initiatives.

To cite this abstract in AMA style:

Hwang H, Kong J, Kim J, Kim Y, Moon J, Jeong K, Park J, Park J, Ban T, Yang J, Ahn C, Lee S. Validation of Single Nucleotide Polymorphisms for Acute Renal Graft Rejection [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/validation-of-single-nucleotide-polymorphisms-for-acute-renal-graft-rejection/. Accessed November 22, 2024.

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