Verification of the Role of ADAMTS13 in the Cardiovascular Disease Using Two-Sample Mendelian Randomization

Overview

Journal Front Genet

Date 2021 Jul 19

PMID 34276770

Citations 6

Authors

Zixiang Ye

Jingang Zheng

Affiliations

Soon will be listed here.

Abstract

Objective: ADAMTS13 plays a crucial role in several diseases. Many observational studies have reported the relationship between ADAMTS13 and some cardiovascular diseases but have drawn different conclusions, likely attributed to confounding factors lacking adjustment. Identifying the role of ADAMTS13 in cardiovascular diseases is pivotal for prevention as well as early intervention in patients with latent cardiovascular diseases. This study aims to estimate whether the level and activity of ADAMTS13 are causally associated with common cardiovascular diseases.

Methods: We applied a two-sample Mendelian randomization approach incorporating genome-wide association summary statistics to verify the causal association between ADAMTS13 level, as well as activity and cardiovascular diseases.

Results: Lower ADAMTS13 activity was causally associated with the increased risks for coronary heart diseases ( = -0.0041, = 0.0019, < 0.05) as well as myocardial infarction ( = -0.0048, = 0.0022, < 0.05). Standard inverse-variance weighted Mendelian randomization results suggested no genetic support for a causal association between ADAMTS13 level and cardiovascular diseases including coronary heart disease, myocardial infarction, atrial fibrillation, heart failure, and venous thromboembolism ( > 0.05).

Conclusion: The causal effect of lower ADAMTS13 activity on the increased odds of having cardiovascular diseases was coronary heart disease and myocardial infarction.

Citing Articles

Causal relationship between dietary salt intake and dementia risk: Mendelian randomization study.

Shi K, Yu Y, Li Z, Hou M, Li X Genes Nutr. 2024; 19(1):6.

PMID: 38491466 PMC: 10943813. DOI: 10.1186/s12263-024-00741-w.

ADAMTS-13 activity in stroke of known and unknown cause: Relation to vascular risk factor burden.

Grosse G, Leotescu A, Sieweke J, Schneppenheim S, Budde U, Ziegler N Front Neurol. 2023; 13:1045478.

PMID: 36703637 PMC: 9871749. DOI: 10.3389/fneur.2022.1045478.

Novel Classification of Thrombotic Disorders Based on Molecular Hemostasis and Thrombogenesis Producing Primary and Secondary Phenotypes of Thrombosis.

Chang J Biomedicines. 2022; 10(11).

PMID: 36359229 PMC: 9687744. DOI: 10.3390/biomedicines10112706.

Genetically predicted phosphate and cardiovascular disease: A Mendelian randomization study.

Huang J, Zhang C, Gong Q, Gao Y, Xie X, Jiang J Front Cardiovasc Med. 2022; 9:973338.

PMID: 36277795 PMC: 9579538. DOI: 10.3389/fcvm.2022.973338.

The relationship between processed meat, red meat, and risk of types of cancer: A Mendelian randomization study.

Wu K, Liu L, Shu T, Li A, Xia D, Sun X Front Nutr. 2022; 9:942155.

PMID: 36204379 PMC: 9530935. DOI: 10.3389/fnut.2022.942155.

References

Zheng X, Chung D, Takayama T, Majerus E, Sadler J, Fujikawa K . Structure of von Willebrand factor-cleaving protease (ADAMTS13), a metalloprotease involved in thrombotic thrombocytopenic purpura. J Biol Chem. 2001; 276(44):41059-63. DOI: 10.1074/jbc.C100515200. View

Wieberdink R, van Schie M, Koudstaal P, Hofman A, Witteman J, de Maat M . High von Willebrand factor levels increase the risk of stroke: the Rotterdam study. Stroke. 2010; 41(10):2151-6. DOI: 10.1161/STROKEAHA.110.586289. View

Danesh J, Wheeler J, Hirschfield G, Eda S, Eiriksdottir G, Rumley A . C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. N Engl J Med. 2004; 350(14):1387-97. DOI: 10.1056/NEJMoa032804. View

Egger M, Davey Smith G, Schneider M, Minder C . Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997; 315(7109):629-34. PMC: 2127453. DOI: 10.1136/bmj.315.7109.629. View

Banno F, Kokame K, Okuda T, Honda S, Miyata S, Kato H . Complete deficiency in ADAMTS13 is prothrombotic, but it alone is not sufficient to cause thrombotic thrombocytopenic purpura. Blood. 2005; 107(8):3161-6. DOI: 10.1182/blood-2005-07-2765. View

Machiela M, Chanock S . LDlink: a web-based application for exploring population-specific haplotype structure and linking correlated alleles of possible functional variants. Bioinformatics. 2015; 31(21):3555-7. PMC: 4626747. DOI: 10.1093/bioinformatics/btv402. View

Zheng J, Baird D, Borges M, Bowden J, Hemani G, Haycock P . Recent Developments in Mendelian Randomization Studies. Curr Epidemiol Rep. 2017; 4(4):330-345. PMC: 5711966. DOI: 10.1007/s40471-017-0128-6. View

Denorme F, Kraft P, Pareyn I, Drechsler C, Deckmyn H, Vanhoorelbeke K . Reduced ADAMTS13 levels in patients with acute and chronic cerebrovascular disease. PLoS One. 2017; 12(6):e0179258. PMC: 5462472. DOI: 10.1371/journal.pone.0179258. View

Lee M, Rodansky E, Smith J, Rodgers G . ADAMTS13 promotes angiogenesis and modulates VEGF-induced angiogenesis. Microvasc Res. 2012; 84(2):109-15. DOI: 10.1016/j.mvr.2012.05.004. View

10.

Maino A, Siegerink B, Lotta L, Crawley J, le Cessie S, Leebeek F . Plasma ADAMTS-13 levels and the risk of myocardial infarction: an individual patient data meta-analysis. J Thromb Haemost. 2015; 13(8):1396-404. DOI: 10.1111/jth.13032. View

11.

Uemura M, Fujimura Y, Ko S, Matsumoto M, Nakajima Y, Fukui H . Pivotal role of ADAMTS13 function in liver diseases. Int J Hematol. 2010; 91(1):20-9. DOI: 10.1007/s12185-009-0481-4. View

12.

Horii M, Uemura S, Uemura M, Matsumoto M, Ishizashi H, Imagawa K . Acute myocardial infarction as a systemic prothrombotic condition evidenced by increased von Willebrand factor protein over ADAMTS13 activity in coronary and systemic circulation. Heart Vessels. 2008; 23(5):301-7. DOI: 10.1007/s00380-008-1053-x. View

13.

Chauhan A, Motto D, Lamb C, Bergmeier W, Dockal M, Plaimauer B . Systemic antithrombotic effects of ADAMTS13. J Exp Med. 2006; 203(3):767-76. PMC: 2118248. DOI: 10.1084/jem.20051732. View

14.

Bowden J, Davey Smith G, Haycock P, Burgess S . Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator. Genet Epidemiol. 2016; 40(4):304-14. PMC: 4849733. DOI: 10.1002/gepi.21965. View

15.

Mazetto B, Orsi F, Barnabe A, de Paula E, Flores-Nascimento M, Annichino-Bizzacchi J . Increased ADAMTS13 activity in patients with venous thromboembolism. Thromb Res. 2012; 130(6):889-93. DOI: 10.1016/j.thromres.2012.09.009. View

16.

Delrue M, Siguret V, Neuwirth M, Joly B, Beranger N, Sene D . von Willebrand factor/ADAMTS13 axis and venous thromboembolism in moderate-to-severe COVID-19 patients. Br J Haematol. 2020; 192(6):1097-1100. DOI: 10.1111/bjh.17216. View

17.

Andersson H, Siegerink B, Luken B, Crawley J, Algra A, Lane D . High VWF, low ADAMTS13, and oral contraceptives increase the risk of ischemic stroke and myocardial infarction in young women. Blood. 2011; 119(6):1555-60. DOI: 10.1182/blood-2011-09-380618. View

18.

Davies N, Holmes M, Davey Smith G . Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians. BMJ. 2018; 362:k601. PMC: 6041728. DOI: 10.1136/bmj.k601. View

19.

Lowe G, Woodward M, Rumley A, Morrison C, Nieuwenhuizen W . Associations of plasma fibrinogen assays, C-reactive protein and interleukin-6 with previous myocardial infarction. J Thromb Haemost. 2003; 1(11):2312-6. DOI: 10.1046/j.1538-7836.2003.00467.x. View

20.

Cines D, Levine L . Thrombocytopenia in pregnancy. Hematology Am Soc Hematol Educ Program. 2017; 2017(1):144-151. PMC: 6142617. DOI: 10.1182/asheducation-2017.1.144. View