Alpha1-antichymotrypsin gene (SERPINA3) A/T polymorphism as a risk factor for aneurysmal subarachnoid hemorrhage

Stroke. 2005 Apr;36(4):737-40. doi: 10.1161/01.STR.0000157598.02014.37. Epub 2005 Feb 17.

Abstract

Background and purpose: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • C-Reactive Protein / metabolism
  • Cathepsin G
  • Cathepsins / metabolism
  • Extracellular Matrix / metabolism
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Inflammation
  • Male
  • Odds Ratio
  • Poland
  • Polymorphism, Genetic*
  • Regression Analysis
  • Risk
  • Risk Factors
  • Serine Endopeptidases / metabolism
  • Subarachnoid Hemorrhage / genetics*
  • alpha 1-Antitrypsin / genetics*

Substances

  • alpha 1-Antitrypsin
  • C-Reactive Protein
  • Cathepsins
  • Serine Endopeptidases
  • CTSG protein, human
  • Cathepsin G