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.
journal_name
Strokejournal_title
Strokeauthors
Yoneyama T,Kasuya H,Onda H,Akagawa H,Hashiguchi K,Nakajima T,Hori T,Inoue Idoi
10.1161/01.STR.0000110788.45858.DCsubject
Has Abstractpub_date
2004-02-01 00:00:00pages
443-8issue
2eissn
0039-2499issn
1524-4628pii
01.STR.0000110788.45858.DCjournal_volume
35pub_type
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