Associations between genetically predicted TIMP-3 levels and risk of venous thromboembolism: A two sample Mendelian randomization study.

Autor: Li Y; Department of Internal Medicine-Cardiovascular, The Second Hospital of Jiaxing, Jiaxing, China., Wang X; Department of Cardiology, Heart Center, The First Affiliated Hospital of Xinxiang Medical University, Weihui, China., Zhang X; Department of Internal Medicine-Cardiovascular, The Second Hospital of Jiaxing, Jiaxing, China., Chen Q; Department of Medicine, The Second Hospital of Jiaxing, Jiaxing, China., Shi X; Cardiovascular Disease Laboratory, The Second Hospital of Jiaxing, Jiaxing, China., Zhang B; Department of Internal Medicine-Cardiovascular, The Second Hospital of Jiaxing, Jiaxing, China., Xu J; Department of Internal Medicine-Cardiovascular, The Second Hospital of Jiaxing, Jiaxing, China. Electronic address: jjxvjx2y@163.com., Han B; Department of Internal Medicine-Cardiovascular, The Second Hospital of Jiaxing, Jiaxing, China. Electronic address: hanbingjiang@163.com.
Jazyk: angličtina
Zdroj: Journal of pharmaceutical and biomedical analysis [J Pharm Biomed Anal] 2024 Sep 15; Vol. 248, pp. 116290. Date of Electronic Publication: 2024 Jun 05.
DOI: 10.1016/j.jpba.2024.116290
Abstrakt: TIMP metallopeptidase inhibitor 3 (TIMP-3) may contribute to the pathogenesis of venous thromboembolism (VTE). However, few studies have investigated the effect of TIMP-3 on VTE. Therefore, a two-sample Mendelian randomization (MR) analysis was conducted to investigate the association between TIMP-3 levels and VTE. Seven independent single-nucleotide polymorphisms (SNPs) for TIMP-3 levels were obtained from a published genome-wide association study (the KORA Consortium, including 997 Europeans). We obtained outcome datasets for VTE, pulmonary embolism (PE), and deep vein thrombosis (DVT) from the FinnGen Consortium. The primary analytical method used in the MR analysis was the inverse variance weighted (IVW) method. To enhance the robustness of the MR results, some other MR methods including weighted median, MR-Egger, and MR-PRESSO were conducted. Moreover, several sensitivity analyses were performed to identify potential horizontal pleiotropy and heterogeneity. In primary IVW MR analyses, per log increase in genetically predicted TIMP-3 levels were positively associated with the incidence of VTE (odds ratio [OR], 1.03; 95 % confidence interval (CI), 1.01, 1.06; P = 0.010), PE (OR, 1.04; 95 % CI, 1.01, 1.08; P = 0.009), and DVT (OR, 1.06; 95 % CI, 1.02, 1.10; P= 0.003). The results of the weighted median, MR-Egger, and MR-PRESSO were similar to the main findings. No unbalanced pleiotropy or heterogeneity was observed. The study suggests that genetically predicted high levels of TIMP-3 may be associated with an increased risk of VTE. These findings indicate that strategies targeting TIMP-3 may provide a basis for the prevention and treatment of VTE. Further investigation is required to clarify this potential mechanism.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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