Abstract 17242: Human Leukocyte Antigen-G Polymorphisms Association to Post Heart Transplant Cardiac Allograft Vasculopathy

Abstract

Introduction: Human Leukocyte Antigen (HLA)-G is an immune inhibitor molecule that has been shown to inhibit smooth muscle cell proliferation in vitro and promote vasculature protection against cardiac allograft vasculopathy (CAV). Single polymorphism nucleotides (SNPs) throughout the gene influence the expression of HLA-G. The association between HLA-G SNPs in heart transplant recipients or donors and CAV remains unclear. Objective: To determine the association between HLA-G SNPs from recipient and donor and severe CAV post heart transplant. Methods: Retrospective cohort in which 251 adult heart transplant recipients and 196 matching donors were evaluated for various HLA-G SNPs. The recipients were screened for CAV according to institutional protocol. Coronary angiographies were graded according to the International Society for Heart and Lung Transplantation classification and severe CAV was defined as 2/3 categories. DNA was genotyped for SNPs 5’ URR 201, 3’ UTR 3196, 3187, 3142 and 14bp INDEL using the Sequenom MassARRAY Platform. The association of genotypes and diagnosis of severe CAV were evaluated in parametric hazard regression model. Results: General characteristics: recipient age 48±12 years, 69% males and donor age 35±14 years. Over a median follow-up of 6 years, 20 (8%) recipients were diagnosed with severe CAV. In multivariable analysis adjusting for donor age, donor cause of death and pre-transplant creatinine, the presence of donor SNP 201 (CC vs TT/TC) was associated with increased risk for severe CAV (HR 5.29; CI 1.70-16.20; p= 0.004), as well as donor SNP 3142 (GG vs CG/CC) was associated (HR 10.05; CI 1.40-71.65; p< 0.02). Furthermore, matching between recipient and donor genotypes at SNP 201 was also associated with increased risk (HR 7.50; CI 2.50-22.39; p< 0.001). Conclusions: Donor HLA-G SNPs 3142/201 and recipient/donor genotype matching for SNP 201 were independent risk factors for the diagnosis of severe CAV. This is the first investigation to identify an association between the HLA-G SNPs mentioned and CAV diagnosis. This association suggests that differences in HLA-G polymorphisms constitute a pathogenic pathway to be explored for potential enhancement of diagnostic, preventive and therapeutic strategies for CAV.