Collagen type I α2 (COL1A2) is the susceptible gene for intracranial aneurysms
Collagen type I α2 (COL1A2) is the susceptible gene for intracranial aneurysms
复制标题
DOI：
10.1161/01.str.0000110788.45858.dc
复制
发表时间：
2004-02-01
期刊：
影响因子：
8.3
通讯作者：
Inoue, I
中科院分区：
文献类型：
--
作者：
Yoneyama, T;Kasuya, H;Inoue, I
背景和目的-染色体7q22.1上的胶原蛋白α 2（I）基因（COL 1A 2）是颅内动脉瘤（IA）的一个位置和功能候选基因，在日本IA患者中广泛筛查其易感性。（包括115例家族性病例）（平均年龄59.9岁）和293例对照（平均年龄61.6岁）。患者和对照组之间等位基因和基因型频率的差异用卡方检验进行评估。用胶原相关肽监测圆二色光谱，该肽用Ala-459和Pro-459模拟I型胶原的三螺旋模型，以估计改变的构象和稳定性。优势比=3.19; 95%CI，2.22至6.50）。该SNP诱导位于三螺旋结构域上的氨基酸459处的Ala至Pro取代。圆二色光谱显示Pro-459肽比Ala-459肽具有更高的热稳定性。结论-COL 1A 2变异可能是有家族史的IA患者的遗传危险因素。
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.