title: Collagen type I alpha2 (COL1A2) is the susceptible gene for intracranial aneurysms.
abstract: OBJECTIVE
  The collagen alpha2(I) gene (COL1A2) on chromosome 7q22.1, a positional and functional candidate for intracranial aneurysm (IA), was extensively screened for susceptibility in Japanese IA patients.
  
  
  METHODS
  Twenty-one single nucleotide polymorphisms (SNPs) of COL1A2 were genotyped in genomic DNA from 260 IA patients (including 115 familial cases) (mean age, 59.9 years) and 293 controls (mean age, 61.6 years). Differences in allelic and genotypic frequencies between the patients and controls were evaluated with the chi(2) test. Circular dichroism spectrometry was monitored with collagen-related peptides that mimic triple-helical models of type I collagen with Ala-459 and Pro-459 to estimate the conformation and stability of alterations.
  
  
  RESULTS
  Significant genotypic association in the dominant model was observed between an exonic SNP of COL1A2 and familial IA patients (chi(2)=11.08; df=1; P=0.00087; odds ratio=3.19; 95% CI, 2.22 to 6.50). This SNP induces Ala to Pro substitution at amino acid 459, located on a triple-helical domain. Circular dichroism spectra showed that the Pro-459 peptide had a higher thermal stability than the Ala-459 peptide.
  
  
  CONCLUSIONS
  The variant of COL1A2 could be a genetic risk factor for IA patients with family history.
authors.affiliation: Department of Neurosurgery, Neurological Institute, Tokyo Women's Medical University, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Yoneyama
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Kasuya
authors.forename: Hideaki
authors.initials: H
authors.lastname: Onda
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Akagawa
authors.forename: Kazunari
authors.initials: K
authors.lastname: Hashiguchi
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Nakajima
authors.forename: Tomokatsu
authors.initials: T
authors.lastname: Hori
authors.forename: Ituro
authors.initials: I
authors.lastname: Inoue
mesh_terms: D002942:Circular Dichroism; D003094:Collagen / Q000235:genetics*; D024042:Collagen Type I; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D015994:Incidence; D002532:Intracranial Aneurysm / Q000453:epidemiology / Q000235:genetics*; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000737:chemistry / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011487:Protein Conformation; D011489:Protein Denaturation / Q000235:genetics; D017678:Sex Distribution
chemical_list: D024042:Collagen Type I; D010455:Peptides; D003094:Collagen