Role of genetics in the development of cardiac allograft vasculopathy

Bratislava Medical Journal

article

Lucie MAYEROVA¹  Anna CHALOUPKA²  Peter WOHLFAHRT³  Jaroslav Alois HUBACEK⁴  Helena BEDANOVA⁵  Zhi CHEN⁶  Josef KAUTZNER¹  Vojtech MELENOVSKY¹  Ivan MALEK¹  Ales TOMASEK⁵  Eva OZABALOVA²  Jan KREJCI²  Tomas KOVARNIK⁷  Milan SONKA⁶  Michal PAZDERNIK¹ 

[1] Department of Cardiology, IKEM;Department of Cardiovascular Diseases, St. Anne’s University Hospital and Masaryk University;Center for Cardiovascular Prevention of the First Faculty of Medicine, Charles University and Thomayer Hospital;Experimental Medicine Centre, Institute for Clinical and Experimental Medicine;Cardiovascular and Transplantation Surgery;Iowa Institute for Biomedical Imaging, The University of Iowa;Department of Internal Medicine, Department of Cardiovascular Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague

关键词: cardiac allograft vasculopathy;    optical coherence tomography;    vascular endothelial growth factor A;    intimal thickening;    genetic polymorphism.;   

DOI  :  10.4149/BLL_2023_031

学科分类：医学（综合）

来源: AEPress, s.r.o.

【 摘 要 】

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).

【 授权许可】

CC BY