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. 2023;124(3):193-200.
doi: 10.4149/BLL_2023_031.

Role of genetics in the development of cardiac allograft vasculopathy

Lucie Mayerova, Anna Chaloupka, Peter Wohlfahrt, Jaroslav Alois Hubacek, Helena Bedanova, Zhi Chen, Josef Kautzner, Vojtech Melenovsky, Ivan Malek, Ales Tomasek, Eva Ozabalova, Jan Krejci, Tomas Kovarnik, Milan Sonka, Michal Pazdernik

Role of genetics in the development of cardiac allograft vasculopathy

Lucie Mayerova et al. Bratisl Lek Listy. 2023.

Abstract

Background: The association between genetic polymorphisms and early cardiac allograft vasculopathy (CAV) development is relatively unexplored. Identification of genes involved in the CAV process may offer new insights into pathophysiology and lead to a wider range of therapeutic options.

Methods: This prospective study of 109 patients investigated 44 single nucleotide polymorphisms (SNPs) within the susceptibility loci potentially related to coronary artery disease, carotid artery intima-media thickness (cIMT), and in nitric oxide synthase gene. Genotyping was done by the Fluidigm SNP Type assays and Fluidigm 48.48 Dynamic Array IFC. The intima thickness progression (IT) was evaluated by coronary optical coherence tomography performed 1 month and 12 months after heart transplantation (HTx).

Results: During the first post-HTx year, the mean intima thickness (IT) increased by 24.0 ± 34.2 µm (p < 0.001) and lumen area decreased by ‒0.9 ± 1.8 mm2 (p < 0.001). The rs1570360 (A/G) SNP of the vascular endothelial growth factor A (VEGFA) gene showed the strongest association with intima thickness progression, even in the presence of the traditional CAV risk factors. SNPs previously related to carotid artery intima-media thickness rs11785239 (PRAG1), rs6584389 (PAX2), rs13225723 (LINC02577) and rs17477177 (CCDC71L), were among the five most significantly associated with IT progression but lost their significance once traditional CAV risk factors had been added.

Conclusion: Results of this study suggest that genetic variability may play an important role in CAV development. The vascular endothelial growth factor A gene SNP rs1570360 showed the strongest association with intima thickness (IT) progression measured by OCT, even in the presence of the traditional CAV risk factors (Tab. 3, Fig. 3, Ref. 36). Text in PDF www.elis.sk Keywords: cardiac allograft vasculopathy, optical coherence tomography, vascular endothelial growth factor A, intimal thickening, genetic polymorphism.

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Figures

Fig. 1.
Fig. 1.. Automated OCT segmentation of coronary wall layers for both M1 and corresponding M12 frames: lumen (red), outer intima (green) and outer media (orange).
Fig. 2.
Fig. 2.. Relative importance of the ten most influential genes associated with intima thickness progression. The higher the feature importance (higher loss in mean absolute error), the higher the influence of a gene on IT progression.
Fig. 3.
Fig. 3.. Relative importance of the most influential risk factors associated with intima thickness progression.
See this image and copyright information in PMC

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