Studying the Association of Melanocortin Receptor-4 Gene Polymorphism and Renal Transplant Rejection
1Renal Division, Transplantation Research Center, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 2Surgery, Perelman School of Medicine University of Pennsylvania, Philadelphia, PA, 3Director Transplant Research Institute, Department of Surgery, The University of Tennessee Health Science Center, Memphis, TN
Meeting: 2019 American Transplant Congress
Abstract number: B54
Keywords: African-American, Gene polymorphism
Session Information
Session Name: Poster Session B: Biomarkers, Immune Monitoring and Outcomes
Session Type: Poster Session
Date: Sunday, June 2, 2019
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall C & D
*Purpose: Accumulating experimental data highlight the importance of targeting the innate immune response to improve transplant outcomes. Inflammation is an unavoidable consequence of transplantation. The intra-graft inflammatory cascade can be initiated following brain death and promoted further by ischemia-reperfusion injuries. A clinical need exists to explore the role of nontraditional regulatory pathways that may exert an important impact on the outcome of transplantation. The regulation of inflammatory responses by the melanocortin system has gained interest recently. Amongst the various melanocortin receptors (MCRs), the importance of MC4R to immune regulation is poorly understood.
*Methods: Here, we investigated the association of a single nucleotide polymorphism (SNPs) of MC4R (rs2229616) with transplant rejection. Genotyping for this SNP was performed using DNA from 167 kidney transplant recipients (mean age of 52 ± 12 years and ~74% African American ethnicity).
*Results: 160 patients had the normal allele (G/G), 3 patients had a heterozygous variant (G/A) and 2 patients had a homozygous variant (A/A) (MAF 0.021). The group of patients with A/A or A/G had a significantly higher rate of transplant rejection, as compared to the G/G group (80% vs. 5%, Chi square p value <0.0001). All five patients within the A/A+A/G group were African American. Excluding the Caucasians, a subset analysis within the African American group revealed a similar increased association of renal transplant rejection with the presence of the A/G or A/A variant (80% vs. 3%, Chi square p value p*<.0001). Then, we examined whether an association exists between this SNP in rs2229616 and rejection in 6,073 Caucasian kidney transplant recipients from The International Genetics & Translational Research in Transplantation Network (iGeneTRAiN). We observed no similar association with biopsy-proven acute rejection within the first 12 months (p = 0.158, MAF = 0.029). Further assessment of these findings in individuals of African ancestry that produced the initial signal will be integral. Therefore, replication efforts are underway to assess this association in >3,400 iGeneTRAiN African American kidney transplant patients.
*Conclusions: These data may provide clues to the higher rate of renal transplant rejection in African Americans.
To cite this abstract in AMA style:
Yilmaz F, Abdi R, Keating BJ, Mas VR. Studying the Association of Melanocortin Receptor-4 Gene Polymorphism and Renal Transplant Rejection [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/studying-the-association-of-melanocortin-receptor-4-gene-polymorphism-and-renal-transplant-rejection/. Accessed May 9, 2025.« Back to 2019 American Transplant Congress