Role of fibrillin-1 genetic mutations and polymorphism in aortic dilatation in patients undergoing intracardiac repair of tetralogy of Fallot.

Objective: The purposes of this study were to identify the occurrence of fibrillin-1 gene polymorphisms or mutations in exons 24 to 28 and to identify the relationship between "DNA sequence variants" and aortic dilatation in the presence of abnormal aortic histopathology and other variables in patients undergoing intracardiac repair of tetralogy of Fallot.

Methods: Operatively excised full-thickness aortic wall tissue and 5 to 10-mL venous blood samples from 74 consecutive patients undergoing intracardiac repair of tetralogy of Fallot were studied. Histopathologic evaluation was done by light microscopy. Polymerase chain reaction amplification of fibrillin-1 gene was carried out for 5 exons (24-28), and amplified products were subjected to single-strand conformation polymorphism analysis to identify sequence alterations, if any. Logistic regression analysis was done to identify the relationship between patients with and without "exonic DNA variants" with other risk factors causing aortic dilatation.

Results: Sixteen aortic tissue specimens (21.6%) were indicated as histologically normal and used as controls. Of 51 patients with dilated aorta, 48 (94.1%) exhibited histologic abnormalities. The incidences of significant lamellar loss, abnormal histopathology, and fibrillin-1 "DNA sequence variants" in tetralogy of Fallot with dilated aorta were 78.4%, 96.1%, and 50.9%, respectively. The risk of aortic dilatation was 8.83 (1.94-13.99) times greater in patients with histologically abnormal aorta and 8.11 (1.93-34.04) times greater in patients with fibrillin-1 "exonic DNA variants."

Conclusion: Our findings indicate the existence of "exonic DNA variants" involving the fibrillin-1 gene in 1 or more exons (exon 24-28). The "DNA sequence variants" are more pronounced in patients with tetralogy of Fallot and dilated aorta in the presence of abnormal aortic histopathology.