Published Online
on January 22, 2004

A more recent version of this article appeared on February 1, 2004

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Submitted on September 18, 2003
Accepted on October 14, 2003

Collagen Type I 2 (COL1A2) Is the Susceptible Gene for Intracranial Aneurysms

Taku Yoneyama MD; Hidetoshi Kasuya MD; Hideaki Onda MD; Hiroyuki Akagawa MD; Kazunari Hashiguchi MD, PhD; Toshiaki Nakajima MD, PhD; Tomokatsu Hori MD; and Ituro Inoue MD^*

From the Department of Neurosurgery, Neurological Institute (T.Y., H.K., H.O., H.A., T.H.) and Maternal and Perinatal Center (K.H.), Tokyo Women’s Medical University; and Division of Genetic Diagnosis, Institute of Medical Science, University of Tokyo (T.Y., H.A., T.N., I.I.), Tokyo, Japan.

^* To whom correspondence should be addressed. E-mail: ituro{at}ims.u-tokyo.ac.jp.

Background and Purpose--The collagen 2(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 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 (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.

Key words: aneurysm • collagen • genetics • subarachnoid hemorrhage

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