O-225 - ANALYSIS OF GENETIC PREDISPOSITION IN ACUTE AORTIC SYNDROME IN NEW ZEALAND

TOPIC:
Thoraco-abdominal Aortic Disease
AUTHORS:
Haran C. (Faculty of Medical and Health Sciences, University of Auckland ~ Auckland ~ New Zealand) , Ghafouri K. (Faculty of Medical and Health Sciences, University of Auckland ~ Auckland ~ New Zealand) , Xu W. (Faculty of Medical and Health Sciences, University of Auckland ~ Auckland ~ New Zealand) , Stiles M. (Genetic Health Service, Auckland District Health Board ~ Auckland ~ New Zealand) , Khashram M. (Department of Vascular Surgery, Waikato Hospital ~ Hamilton ~ New Zealand)
Introduction:
The natural history and progression of acute aortic syndrome (AAS) has been suggested to be more severe in patients with a familial history or a syndromic AAS. (1) One of these being aortic dissection, in which the underlying aetiology is autosomal dominant gene variants in the heritable thoracic aortic disease (HTAD) genes. In New Zealand, large ethnic disparities in the presentation and incidence for patients presenting with AAS have been documented. (2) Despite the underlying risk factors, we postulate there may be an increased genetic predisposition in select patient cohorts. The aim of this study was to analyse genetic variances in patients presenting with AAS.
Methods:
A prospective study of high risk patients having an AAS event were included from May 2021 to April 2022 from the Midland region of New Zealand. All patients under the age of 70 with an AAS were initially included. Patients were then invited to participate for genetic testing if at least one of the following criteria was fulfilled: age of disease onset ≤ 50 years and/or presence of a first-degree relative with aortic aneurysm or dissection. (3) After obtaining informed and written patient consent, blood gene analysis was sent to a genetics laboratory for analysis.
Results:
Since May 2021 to April 2022, 50 patients have been considered for genetic blood sampling. Genetic blood testing has been completed in 32 patients, and of those 18 patients have yielded a positive primary or additional result. Of the 32 patients, 27 patients had a positive history for a concerning family history of genetic abnormality. Of the 18 patients who yielded a positive primary result, 8 had a pathogenic result and 10 have yielded a variant of uncertain significance. The commonest genetic abnormalities found were in the gene FBN1 (n = 5), ACTA2 (n = 3), and SMAD6 (n = 2). There were ethnicity differences, with 50% (7/14) New Zealand European and 63% (10/16) Māori having a positive result, which was not statistically significant (p = 0.56).
Conclusion:
Almost half of the patients tested after having an AAS yielded a positive result. Genetic predisposition as an underlying risk factor for the development of AAS may be overlooked in the New Zealand cohort. This raises the question of furthering genetic testing in a widespread population though there are implications on incidental findings.
References:
1. Shalhub S, Rah J, Campbell R, Sweet M, Quiroga E, Starnes B. Characterization of syndromic, nonsyndromic familial, and sporadic type B aortic dissection. J Vasc Surg. 2021 Jun;73(6):1906-1914.e2. 2. Xu W, Mani K, Khashram M. Ethnic differences in incidence and outcomes of acute aortic syndromes in the Midland region of New Zealand. J Vasc Surg. 2022 Feb;75(2):455-463.e2. 3. National Health Service. National Genomic Test Directory. Great Britain: National Health Service; August 2020. 379.