Division of Health, Sciences, and Technology, Massachusetts Institute of Technology and Harvard Medical School, Boston, Massachusetts.
Division of Hemostasis and Thrombosis, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
Semin Thromb Hemost. 2024 Mar;50(2):188-199. doi: 10.1055/s-0043-1769079. Epub 2023 May 18.
Tissue factor (TF) is the primary initiator of blood coagulation in humans. As improper intravascular TF expression and procoagulant activity underlie numerous thrombotic disorders, there has been longstanding interest in the contribution of heritable genetic variation in , the gene encoding TF, to human disease. This review seeks to comprehensively and critically synthesize small case-control studies focused on candidate single nucleotide polymorphisms (SNPs), as well as modern genome-wide association studies (GWAS) seeking to discover novel associations between variants and clinical phenotypes. Where possible, correlative laboratory studies, expression quantitative trait loci, and protein quantitative trait loci are evaluated to glean potential mechanistic insights. Most disease associations implicated in historical case-control studies have proven difficult to replicate in large GWAS. Nevertheless, SNPs linked to , such as rs2022030, are associated with increased mRNA expression, monocyte TF expression after endotoxin exposure, and circulating levels of the prothrombotic biomarker D-dimer, consistent with the central role of TF in the initiation of blood coagulation.
组织因子（TF）是人类血液凝固的主要启动因子。由于血管内 TF 表达不当和促凝活性是许多血栓形成性疾病的基础，因此人们一直对编码 TF 的 基因中的遗传变异对人类疾病的贡献感兴趣。这篇综述旨在全面、批判性地综合关注候选单核苷酸多态性（SNP）的小型病例对照研究，以及旨在发现变异与临床表型之间新关联的现代全基因组关联研究（GWAS）。在可能的情况下，评估相关的实验室研究、表达数量性状基因座和蛋白质数量性状基因座，以深入了解潜在的机制。历史病例对照研究中涉及的大多数疾病关联在大型 GWAS 中都难以复制。然而，与 相关的 SNPs，如 rs2022030，与增加的 mRNA 表达、内毒素暴露后单核细胞 TF 表达和促血栓生物标志物 D-二聚体的循环水平相关，这与 TF 在血液凝固启动中的核心作用一致。
