O-152 - GENETIC FINDINGS AND RISK VARIANTS IN STANFORD TYPE B AORTIC DISSECTIONS

TOPIC:
Thoraco-abdominal Aortic Disease
AUTHORS:
Erhart P. (Department of Vascular and Endovascular Surgery ~ Heidelberg ~ Germany) , Grond-Ginsbach C. (Department of Vascular and Endovascular Surgery ~ Heidelberg ~ Germany) , Körfer D. (Department of Vascular and Endovascular Surgery ~ Heidelberg ~ Germany) , Böckler D. (Department of Vascular and Endovascular Surgery ~ Heidelberg ~ Germany)
Introduction:
Pathogenic mutations or genetic risk variants are known to cause or elevate the risk for Stanford type B aortic dissections (STBAD). Genetic diagnostics and counselling should be offered to young patients (< 40 years at disease onset) or a positive familial history for thoracic aortic disease. The presentation will highlight the current genetical background in STBAD patients and prospects to improve clinical precision medicine.
Methods:
From 2008 to 2022 we consecutively enrolled 148 patients with Stanford type B aortic dissections. Next generation sequencing was used to identify pathogenic variants in protein-coding sequences and to identify relevant copy number variations (CNV). Variants in a predefined panel of 30 candidate genes for thoracic aortic aneurysms and dissections (TAAD) were evaluated. In addition, a currently reported genetic single nucleotide risk variant (rs1172113) in LRP1 (low-density lipoprotein receptor-related protein 1) was analysed in all patients and related to the clinical disease outcome.
Results:
In 9 patients with STBAD onset < 40 years of age, next generation sequencing analysis revealed causal novel variants in fibrillin-1 (FBN1) in three patients and a large copy number variation on chromosome 10 deleting eleven genes, including ACTA2 (actin alpha 2) gene in another patient. Furthermore, variants of unknown significance in MYLK (myosin light chain kinase), CBS (cystathionine beta-synthase), PKD1 (polycystic kidney disease 1) and COL3A1 (collagen type III alpha 1 chain) were detected. The LRP1 single nucleotide (rs1172113) risk variation was an independent risk factor for STBAD (p= 0.002) after sex and age adjustment in a logistic regression model analysing diabetes, smoking and hypertension as additional risk factors. Patients with the LRP1 risk allele were more likely to develop aorta-related complications (risk allele 75.6% vs. 63.8%; p= 0.002) during a median follow-up of 2.0 years.
Conclusion:
In accordance to the ESVS clinical practice guidelines genetic counselling should be offered in patients < 40 years with sporadic STBAD and individuals with suspected familial inheritance for TAAD. The LRP1 genetic risk variation was confirmed to be an independent risk factor for STBAD that might be associated with a worse clinical outcome and more aorta-related complications. These results encourage clinicians to perform genetic diagnostics in STBAD patients to detect novel genetic variants, perform genetic counselling of family members and improve precision medicine.