Role of Genetics in Development of Cardiac Allograft Vasculopathy

Purpose Even though a wide range of cardiac allograft vasculopathy (CAV) risk factors have been identified, the real genesis of this disease remains elusive. Identification of genes involved in the process of CAV may provide a novel insight on pathophysiology and lead to new therapeutic options. Methods Paired single nucleotide polymorphism (SNP) genotyping using custom-designed chip from Fluidigm Corp. was performed in both heart transplant (HTx) donors and recipients. DNA analysis included 44 SNPs selected within the susceptibility loci potentially related to coronary artery disease, carotid artery intima-media thickness (IMT), and in nitric oxide synthase gene. For CAV assessment, coronary OCT imaging was performed at 1 month and 12 months after HTx. Results A total of 38 consecutive patients with paired genotyping and OCT studies were included. During the first post-transplant year, significant reduction in the mean luminal area (p = 0.028) and progression in mean intimal thickness (p = 0.001) were observed. In the random forest analysis, HTx recipient ADAMTS7 (rs3825807) and CBFA2T3 (rs844396) loci showed best association with coronary intimal thickness progression (Image). These loci were previously reported to be involved in the process of coronary atherosclerosis and carotid IMT progression. Conclusion Genetic variability may play an important role in CAV development. Identification of risk alleles associated with accelerated CAV may be useful in CAV risk stratification and post-transplant management individualisation. This project was supported by following national research grants (CMH 16-27465A and NIH R01-EB004640).