Dudra Ján, Lindner Jaroslav, Vaněk Ivan, Simova Jana, Mazura Ivan, Miler Ivo, Ciháková Jana, Capek Pavel, Belák Josef
Department of Surgery, Municipal Hospital Kutna Hora, Kutná Hora;
Int J Angiol. 2009 Summer;18(2):99-102. doi: 10.1055/s-0031-1278335.
Approximately 10% of patients who undergo surgery for aortic valve disease (stenosis or regurgitation) suffer from ascending aortic dilation (AAD). A possible genetic etiology of AAD associated with aortic valve disease has been repeatedly mentioned in the literature, but a specific responsible gene mutation has not been described.
In the present study, two groups of patients were compared, all of whom underwent surgery for aortic valve disease. Group A was a cohort of 27 patients who suffered from aortic valve disease associated with AAD. Group B was a cohort of 29 patients with structural aortic valve disease, but without concomitant AAD (control group). Genomic DNA was extracted from the white blood cells of peripheral blood samples and was amplified using primers specific for chosen exons of the fibrillin-1 gene, including their intron/exon boundaries. Exons 26 and 27 were selected for analysis.
Analysis of the intronic part situated close to exon 27 showed insertion of cytosine between nucleotide 37 682 and 37 683 of query sequence. This insertions was classified as IVS 37 682 and 37 683insC. This mutation was found in all 27 patients from group A (patients with structural aortic valve disease accompanied by significant AAD). The abovementioned mutation was not found in any of the 29 patients from group B.
This finding has potential implications for risk stratification and therapeutic targeting not only for patients with existing disease, but also for the general population. Future studies are needed to determine the clinical utility of the finding; however, the present hypothesis needs to be verified by further molecular studies.
接受主动脉瓣疾病（狭窄或反流）手术的患者中，约10%患有升主动脉扩张（AAD）。文献中多次提及与主动脉瓣疾病相关的AAD可能的遗传病因，但尚未描述具体的致病基因突变。
在本研究中，比较了两组均接受主动脉瓣疾病手术的患者。A组为27例患有与AAD相关的主动脉瓣疾病的患者队列。B组为29例患有结构性主动脉瓣疾病但无合并AAD的患者队列（对照组）。从外周血样本的白细胞中提取基因组DNA，并使用针对原纤维蛋白-1基因选定外显子（包括其内含子/外显子边界）的引物进行扩增。选择外显子26和27进行分析。
对靠近外显子27的内含子部分进行分析显示，在查询序列的第37682和37683个核苷酸之间插入了胞嘧啶。此插入被分类为IVS 37682和37683insC。在A组的所有27例患者（患有伴有明显AAD的结构性主动脉瓣疾病患者）中均发现了这种突变。在B组的29例患者中均未发现上述突变。
这一发现不仅对现有疾病患者，而且对普通人群的风险分层和治疗靶点都具有潜在意义。需要进一步的研究来确定这一发现的临床实用性；然而，目前的假设需要通过进一步的分子研究来验证。
