05949769-c3d5-4f53-83c5-5affd2db49bb
title
Collagen type I alpha2  ( COL1A2 ) is the susceptible gene for intracranial aneurysms.
ede4ef5d-451f-4904-8cb7-e97bf4c80b86
abstract
BACKGROUND AND PURPOSE: 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.