Study Of Matrix Metalloproteinase (mmp) And Tissue Inhibitors Of Metalloproteinase (timp) Gene Polymorphisms In Renal Allograft Outcome
1Department of Immunopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India, 2Department of Renal Transplant Surgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India, 3Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India, 4Department of Nephrology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
Meeting: 2022 American Transplant Congress
Abstract number: 9049
Keywords: Gene polymorphism, Kidney transplantation, Metalloproteinases, Rejection
Topic: Basic Science » Basic Science » 11 - Histocompatibility and Immunogenetics
Session Information
Session Name: Histocompatibility and Immunogenetics
Session Type: Poster Abstract
Date: Sunday, June 5, 2022
Session Time: 7:00pm-8:00pm
Presentation Time: 7:00pm-8:00pm
Location: Hynes Halls C & D
*Purpose: Our study aimed to find a role, if any, of functional gene polymorphisms of MMP and their inhibitors- TIMP in renal allograft outcome.
*Methods: The data of patients who underwent renal transplant in a tertiary care center from January 2003 to December 2018 were reviewed. They were divided into two groups-Rejecters(n=100) and Non-Rejecters(n=100)-based on the histopathological diagnosis of transplant rejection within one year after transplantation. Among the rejectors, 31 had graft loss. Endpoint genotyping (KASP® SNP Genotyping system, LGC Genomics, UK) was used to study six single nucleotide polymorphisms (SNP) viz MMP1 -1607 1G>2G, MMP2 -735 C>T, MMP9 2003G>A, MMP9 1721G>C, TIMP1 536C>T and TIMP2 303C>T.
*Results: The study included 100 rejecters (87 men and 13 women, mean age- 36.3±12.2 years) and 100 non-rejecters (85 men and 15 women, mean age- 33.9±11.2 years). TIMP2 303C>T SNP analysis showed TT genotype was significantly associated with rejection and graft loss while CT genotype significantly associated with stable graft. When the graft loss group was compared with non rejectors, there was a significant difference (Refer table). The rejection free allograft survival was analyzed in patients who had at least one episode of rejection during follow up (n=108, including rejecters and 8 non-rejecters who had rejection episodes after 1 year of transplant) using the Mantel Cox log rank test for the TIMP2 303C>T polymorphism. The median time to first rejection was significantly lower (p value < 0.001) in TT genotype (3 weeks) compared to CC genotype (52 weeks). The other gene polymorphisms studied did not show significant difference (p>0.05) between the rejecters and non-rejecters.
*Conclusions: The TT genotype of TIMP2 303C>T SNP was significantly associated with graft rejection and graft loss in our patients while CT genotype clearly associated with stable grafts. It is found that in those with atleast one rejection vs those with no rejection, TT genotype of TIMP2 303C>T SNP was significantly associated and caused earlier rejections. These findings should be validated in higher powered studies.
To cite this abstract in AMA style:
Tom JP, Singh J, Sharma A, Aggarwal R, Nada R, Ramachandran R, Anand S, Minz R. Study Of Matrix Metalloproteinase (mmp) And Tissue Inhibitors Of Metalloproteinase (timp) Gene Polymorphisms In Renal Allograft Outcome [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/study-of-matrix-metalloproteinase-mmp-and-tissue-inhibitors-of-metalloproteinase-timp-gene-polymorphisms-in-renal-allograft-outcome/. Accessed November 21, 2024.« Back to 2022 American Transplant Congress