Is there any association between rs1303 (Pi*M3) variant of alpha-1 antitrypsin gene and atrial septal aneurysm development?

Aim Atrial septal aneurysm (ASA) is one of the congenital heart defects. The underlying pathophysiology of ASA has not been fully understood yet. Alpha-1 antitrypsin (A1AT) is a serine protease inhibitor glycoprotein, which is held responsible from tissue wall proteolysis if it is deficient in the body. The aim of this study was to investigate A1AT serum levels and the rs1303 (Pi*M3) variant in A1AT gene in patients with ASA. Material and Methods Thirty patients (7 male and 23 female) with isolated ASA and 33 patients (11 male and 22 female) with normal atrial septum on echocardiography were included in this study. A1AT serum levels of study patients were measured quantitatively by the enzyme-linked immune sorbent assay (ELISA) method. The A1AT gene mutation rs1303 was analyzed by genotyping, which is performed on genomic DNA extracted from circulating mononuclear blood cells. Single-nucleotide polymorphism was evaluated on polymerase chain reaction using commercial kits. Results A1AT serum levels were not statistically different among patients with and without ASA (9.52 +/- 4.33 mu g/mL vs 9.83 +/- 5.27 mu g/mL, respectively, P = .80). A1AT homozygote mutation (PiM3M3) was significantly higher in the ASA group than the control group (21 vs 11, OR (95% CI): 6.68 [2.09-21.40], P = .001). A1AT serum levels were similar among patients with normal A1AT allele (PiMM), homozygote variant (PiM3M3), and heterozygote variant (PiMM3) (P = .79). Conclusion This preliminary study revealed that homozygote A1AT rs1303 (PiM3M3) variant is significantly higher in patients with isolated ASA and may be associated with ASA development. Large scale comprehensive studies are needed to validate these results.