Forensic pathological study of relationship between cerebral aneurysm and type III collagen

应用免疫组织化学方法对5例脑动脉瘤破裂患者脑动脉瘤壁中III型和I型胶原的分布进行了分析。瘤壁由增厚的内、外膜组成，抗I型胶原抗体免疫组化染色，抗III型胶原抗体淡染。III型胶原主要分布于脑动脉的中层和外膜。脑动脉壁内III型胶原的分布与无动脉瘤组无明显差异。我们研究了III型胶原基因(COL3A1)外显子31的G-A多态和外显子33的C-T多态与脑动脉瘤的关系。从84例因病猝死的患者中提取DNA。脑动脉瘤破裂组(6例)外显子33 C等位基因频率为0.08，T等位基因频率为0.92，而对照组(58例心脏性猝死)C等位基因频率为0.05，T等位基因频率为0.95。脑动脉瘤破裂组外显子31的G等位基因和A等位基因频率分别为0.58和0.42，对照组分别为0.58和0.42。动脉疾病组(脑动脉瘤、主动脉瘤、脑出血20例)中，C等位基因和T等位基因的等位基因频率分别为0.12和0.88，G等位基因和A等位基因的等位基因频率分别为0.5和0.5。脑动脉瘤破裂组和动脉疾病组的C等位基因频率均高于对照组，而外显子31和外显子33的C等位基因频率在三组间均无显著差异。提示COL3A1基因外显子33的突变可能与脑动脉瘤破裂有关。

The distribution of type III and type I collagen in the wall of cerebral aneurysms was analyzed immunohistochemically in 5 victims due to rupture of cerebral aneurysm. The wall of the aneurysms consisted of thickened intima and adventitia, which were immunostained with anti-type I collagen antibody, and were lightly stained with anti-type III collagen antibody. The type III collagen were distributed in the media and adventitia of the cerebral arteries. There were no marked difference in the distribution of type III collagen between in the wall of cerebral arteries with aneurysm and in that of those without aneurysm. These findings show that the wall of aneurysm consist mainly of type I collagen.We studied relationship between polymorphisms of type III collagen gene (COL3A1), i.e., G to A polymorphism in exon 31 and C to T in exon 33, and cerebral aneurysm. DNA was extracted from 84 cases of sudden deaths due to illness. The gene frequency of C-allele and T-allele in exon 33 were 0.08 and 0.92 in the group of rupture of cerebral aneurysm (6 cases), while these were 0.05 and 0.95 in the control group (58 of sudden cardiac deaths), respectively. Those of G-allele and A-allele in exon 31 were 0.58 and 0.42 in the group of rupture of cerebral aneurysm, while these were 0.58 and 0.42 in the control group, respectively. In the group of arterial diseases (20 cases of cerebral aneurysm, aortic aneurysm or cerebral hemorrhage), those of C-allele and T-allele were 0.12 and 0.88, and those of G-allele and A-allele were 0.5 and 0.5, respectively. The frequencies of C-allele in the group of rupture of cerebral aneurysm and in the group of arterial diseases were higher than that in the control group, though there were no significant differences in those both in exon 31 and in exon 33 among the three groups. These results suggest that the mutation in exon 33 of COL3A1 may relate to rupture of cerebral aneurysms.