Identification of COL3A1 variants associated with sporadic thoracic aortic dissection: a case-control study
Identification of COL3A1 variants associated with sporadic thoracic aortic dissection: a case-control study
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与散发性胸主动脉夹层相关的 COL3A1 变异的鉴定：病例对照研究
DOI：
10.1007/s11684-020-0826-1
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发表时间：
2021-05-28
影响因子：
8.1
通讯作者：
Wang, Dao Wen
中科院分区：
文献类型：
--
作者：
Chen, Yanghui;Sun, Yang;Wang, Dao Wen
没有家族聚集性或综合征特征的胸主动脉夹层称为散发性夹层。到目前为止，STAD的遗传基础仍然未知。对来自中国汉族人群的223例STAD患者和414例健康对照（N = 637）进行全外显子组测序。在对群体结构、亲缘关系和家系分析的基础上，采用最优序列核关联检验对STAD的候选基因或变异体进行了鉴定。经10000次排列检验（P = 2.49 × 10（-3）），发现COL 3A 1与STAD显著相关（P = 7.35 × 10（-6））。此外，另一个独立队列，包括423例病例和734例非STAD受试者（N = 1157），复制了我们的结果（P = 0.021）。进一步的生物信息学分析表明，COL 3A 1在主动脉夹层组织中高表达，其表达与细胞外基质（ECM）通路有关。我们的研究确定了中国STAD人群中已知的可遗传TAD基因谱，并发现COL 3A 1可以通过ECM途径增加STAD的风险。我们希望扩大对STAD的遗传基础和病理学的了解，这可能有助于为患者提供更好的遗传咨询。
Thoracic aortic dissection (TAD) without familial clustering or syndromic features is known as sporadic TAD (STAD). So far, the genetic basis of STAD remains unknown. Whole exome sequencing was performed in 223 STAD patients and 414 healthy controls from the Chinese Han population (N = 637). After population structure and genetic relationship and ancestry analyses, we used the optimal sequence kernel association test to identify the candidate genes or variants of STAD. We found that COL3A1 was significantly relevant to STAD (P = 7.35 x 10(-6)) after 10 000 times permutation test (P = 2.49 x 10(-3)). Moreover, another independent cohort, including 423 cases and 734 non-STAD subjects (N = 1157), replicated our results (P = 0.021). Further bioinformatics analysis showed that COL3A1 was highly expressed in dissected aortic tissues, and its expression was related to the extracellular matrix (ECM) pathway. Our study identified a profile of known heritable TAD genes in the Chinese STAD population and found that COL3A1 could increase the risk of STAD through the ECM pathway. We wanted to expand the knowledge of the genetic basis and pathology of STAD, which may further help in providing better genetic counseling to the patients.