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J Heart Lung Transplant. 2016 Sep;35(9):1101-7. doi: 10.1016/j.healun.2016.04.014. Epub 2016 May 6.

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

Author information

1
Division of Cardiovascular Surgery.
2
Division of Cardiology, Peter Munk Cardiac Centre, Toronto General Hospital-University Health Network, Toronto, Ontario, Canada.
3
Division of Cardiology, Peter Munk Cardiac Centre, Toronto General Hospital-University Health Network, Toronto, Ontario, Canada. Electronic address: diego.delgado@uhn.on.ca.

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.

KEYWORDS:

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

PMID:
27287629
DOI:
10.1016/j.healun.2016.04.014
[Indexed for MEDLINE]

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