TIMP-1 c.T372C遺伝子多型による急性大動脈解離の予測可能性

While single nucleotide polymorphisms (SNP) have been extensively researched in atherosclerotic aortic aneurysms, there are too few data about acute aortic dissection (AAD). The matrix metalloproteinase regulation system has shown a high biological relevance to the development of aortic aneurysms and AAD. The TIMP-1 c.T372C (rs4898, nt+434) SNP was previously associated with the onset of abdominal aortic and other aneurysms. Therefore, we chose this SNP to search for a connection with AAD and to find its place among the other risk factors. 115 patients with AAD were studied for their TIMP-1 c.T372C genotype by means of conventional restrictase analysis. To confirm the biological relevance of our findings, immunohistochemistry for TIMP-1 was performed on tissue samples from the same patients with AAD and compared with a control group of 23 autopsy cases. The TIMP-1 c.T372C showed a significant difference in allele frequency in the AAD patients compared to the general population (p < 0.0001 for both sexes). This genotype did not show any association with any other co-morbid condition, nor with age. The immunohistochemistry results also showed significantly lower TIMP-1 expression in the dissected aortas. The C allele of TIMP-1 c.T372C shows a strong association with the onset of AAD.広島大学(Hiroshima University)博士(医学)Philosophy in Medical Sciencedoctora