Alpha1-antichymotrypsin gene (SERPINA3) A/T polymorphism as a risk factor for aneurysmal subarachnoid hemorrhage.
OBJECTIVE
The member 3 of clade A of serine proteinase inhibitors (SERPINA3), known previously as the alpha1-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.


CONCLUSIONS
The A/T polymorphism of SERPINA3 gene is associated with the risk factor for aneurysmal SAH.
Slowik
Agnieszka
A
Department of Neurology, Jagiellonian University, Krakow, Poland. slowik@neuro.cm-uj.krakow.pl
Borratynska
Anna
A
Turaj
Wojciech
W
Pera
Joanna
J
Dziedzic
Tomasz
T
Figlewicz
Denise A
DA
Betlej
Marek
M
Krzyszkowski
Tadeusz
T
Czepko
Ryszard
R
Szczudlik
Andrzej
A
D000483:Alleles; D002097:C-Reactive Protein / Q000378:metabolism; D056649:Cathepsin G; D002403:Cathepsins / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007249:Inflammation; D008297:Male; D016017:Odds Ratio; D011044:Poland; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D012306:Risk; D012307:Risk Factors; D012697:Serine Endopeptidases / Q000378:metabolism; D013345:Subarachnoid Hemorrhage / Q000235:genetics*; D000515:alpha 1-Antitrypsin / Q000235:genetics*
D000515:alpha 1-Antitrypsin; D002097:C-Reactive Protein; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G