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

Julieta Lazarte, Livia Goldraich, Cedric Manlhiot, Filio Billia, Heather Ross, Vivek Rao, Diego Delgado

Research output: Contribution to journalArticlepeer-review

Abstract

Background 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. Methods 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. Results 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). Conclusions 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.

Original languageEnglish (US)
Pages (from-to)1101-1107
Number of pages7
JournalJournal of Heart and Lung Transplantation
Volume35
Issue number9
DOIs
StatePublished - Sep 1 2016

Keywords

  • HLA
  • HLA-G polymorphisms
  • cardiac allograft vasculopathy
  • graft vasculopathy
  • heart transplantation
  • immune system
  • tolerance

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation

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