α1-antichymotrypsin gene (SERPINA3) A/T polymorphism as a risk factor for aneurysmal subarachnoid hemorrhage

Background and Purpose - The member 3 of clade A of serine proteinase inhibitors (SERPINA3), known previously as the alpha(1)-antichymotrypsin, is an acute phase protein, the levels of which increase in acute and chronic inflammation. The A/T polymorphism of the SERPINA3 gene influences expression of SERPINA3 protein. SERPINA3 can be related to aneurysmal subarachnoid hemorrhage (SAH) by influencing inflammation or by regulating cathepsin G activity. We studied the significance of SERPINA3 A/T polymorphism in patients with aneurysmal SAH compared with healthy controls. Methods - A total of 180 patients with aneurysmal SAH and 263 healthy controls were genotyped for the SERPINA3 A/T polymorphism. Aneurysmal SAH was diagnosed by cranial computed tomography or lumbar puncture and digital subtraction angiography. SERPINA3 polymorphism was detected by polymerase chain reaction amplification and restriction enzyme digestion. Results - The SERPINA3 genotype distribution in patients with aneurysmal SAH (AA-29 16.1%; AT-108 60.0%; TT-43 23.9%) differed significantly from controls (AA-70 26.6%; AT-123 46.8%; TT- 70 26.6%; P = 0.009). A logistic regression model showed that the presence of genotype with T allele ( AT + TT; odds ratio [ OR], 2.01; 95% CI, 1.19 to 3.38; P = 0.009) or AA genotype ( OR, 0.49; 95% CI, 0.30 to 0.84; P = 0.009) of the SERPINA3 influences the risk for aneurysmal SAH independently from smoking, excessive alcohol consumption, and hypertension. Conclusion - The A/T polymorphism of SERPINA3 gene is associated with the risk factor for aneurysmal SAH.