Human leukocyte antigen G single-nucleotide polymorphism -201 (CC–CC) donor–recipient genotype matching as a predictor of severe cardiac allograft vasculopathy

Abstract

In heart transplant recipients, human leukocyte antigen G (HLA-G) has been shown to inhibit endothelial and smooth muscle cells injury in vitro, suggesting protection against cardiac allograft vasculopathy (CAV). Although the expression of HLA-G is regulated by single-nucleotide polymorphisms (SNPs), their association with CAV remains unknown. Therefore, the objective of this study was to determine the association between recipient and donor HLA-G SNPs with CAV. We retrospectively analyzed DNA for HLA-G SNPs of 251 adult heart recipients, 196 of whom had their corresponding donors included. Severe CAV was defined as ISHLT Category 2 or 3. The association between donor-recipient genotypes and diagnosis of severe CAV over time was evaluated with parametric hazard regression models. Recipient age was 48 ± 12 years, whereas donor age was 35 ± 14 years. Median follow-up was 5.0 years (range 1 day to 13.2 years). At 10 years after transplantation, freedom from severe CAV, retransplantation or death was 64%. In multivariable analysis adjusted for donor age, recipient weight and pre-transplant Class II antibodies, the presence of donor-recipient SNP -201 (CC-CC) matching was associated with an increased risk of severe CAV (hazard ratio 11.9; 95% confidence interval 4.3 to 32.9; p < 0.001). Matching of donor-recipient SNP -201 (CC-CC) was an independent risk factor for the diagnosis of severe CAV. HLA-G SNP genotypes may reveal a pathogenic pathway to be explored for diagnostic and therapeutic strategies for CAV.