Identification of COL3A1 variants associated with sporadic thoracic aortic dissection: a case--control study

Abstract

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 × 10⁻⁶) after 10 000 times permutation test (P = 2.49 × 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.

Keywords

sporadic thoracic aortic dissection / exome sequencing / gene COL3A1 / case–control study / extracellular matrix

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Nos. 91839302, 91439203, and 81700413), the National Key R&D Program of China (No. 2017YFC0909400), and the Municipal Science and Technology Major Project (No. 2017SHZDZX01).

Compliance with ethics guidelines

Yanghui Chen, Yang Sun, Zongzhe Li, Chenze Li, Lei Xiao, Jiaqi Dai, Shiyang Li, Hao Liu, Dong Hu, Dongyang Wu, Senlin Hu, Bo Yu, Peng Chen, Ping Xu, Wei Kong, and Dao Wen Wang declare that they have no conflicts of interest. All procedures were performed in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study.

Electronic Supplementary Material

Supplementary material is available in the online version of this article at https://doi.org/ 10.1007/s11684-020-0826-1 and is accessible for authorized users.

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