Article Text

PDF
Research paper
Association between the rs1333040 polymorphism on the chromosomal 9p21 locus and sporadic brain arteriovenous malformations
  1. Carmelo Lucio Sturiale1,
  2. Ilaria Gatto2,
  3. Alfredo Puca1,
  4. Sonia D'Arrigo3,
  5. Igor Giarretta2,
  6. Alessio Albanese1,
  7. Concezio Di Rocco1,
  8. Giulio Maira1,
  9. Roberto Pola2,4
  1. 1Department of Neurosurgery, Catholic University School of Medicine, Rome, Italy
  2. 2Department of Medicine, Laboratory of Vascular Biology and Genetics, Catholic University School of Medicine, Rome, Italy
  3. 3Department of Anaesthesiology and Intensive Care, Catholic University School of Medicine, Rome, Italy
  4. 4Division of Cardiovascular Research, Department of Medicine, St Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA
  1. Correspondence to Dr C L Sturiale, Institute of Neurosurgery, Catholic University School of Medicine, L go A Gemelli 8, Rome 00168, Italy; cropcircle.2000{at}virgilio.it

Abstract

Background Single nucleotide polymorphisms (SNPs) on chromosome 9p21 have been recently associated with intracranial aneurysms and stroke. In this study, we tested the association between the rs1333040C>T polymorphism on the 9p21 locus and sporadic brain arteriovenous malformations (BAVMs).

Methods We studied 78 patients with sporadic BAVMs and 103 unaffected controls. Genomic DNA was isolated from peripheral blood and the rs1333040C>T polymorphism was assessed by PCR–restriction fragment length polymorphism using the BsmI restriction endonuclease.

Results We found that the distribution of the three genotypes (TT/TC/CC) of the rs1333040 polymorphism was significantly different between cases and controls (p=0.02). Using dominant, recessive and additive genetic models, we found that the TT genotype and the T allele were significantly more common in the BAVM group than in controls. We also evaluated whether the rs1333040 polymorphism was associated with prototypical angio-architectural features of BAVMs (such as nidus size, venous drainage pattern and Spetzler–Martin grading) and with the occurrence of seizures and bleeding. We detected a significant association between the homozygous T allele in the recessive model and BAVMs with a nidus >4 cm in diameter. Deep venous drainage was significantly more frequent among subjects carrying at least one T allele in the dominant model. Patients with seizures showed a significant association with the TT genotype and the T allele in all genetic models examined whereas those who experienced intracranial bleeding showed a significant association with the T allele in the trend model.

Conclusions This is the first study demonstrating an association between an SNP of the 9p21 region and sporadic BAVMs. Our results emphasise the relevance of this chromosomal locus as a common risk factor for various forms of cerebrovascular diseases.

  • CEREBROVASCULAR DISEASE
  • GENETICS
  • NEUROGENETICS

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.