Department of Joint Surgery, Honghui Hospital,Xi'an Jiaotong University.
Department of Traumatic Orthopedics, Honghui Hospital, Xi'an Jiaotong University.
J Atheroscler Thromb. 2021 Mar 1;28(3):293-303. doi: 10.5551/jat.56333. Epub 2020 Jun 24.
Deep vein thrombosis (DVT) is a common complication of orthopedic surgery. Multiple lines of evidence indicate that genetic factors play an important role in the development of DVT following orthopedic surgery (DVTFOS). Recent evidence suggested that the solute carrier family 44 member 2 (SLC44A) gene may contribute to the risk of DVT. In this study, we aimed to investigate the associations of SLC44A2 and DVTFOS in Chinese Han individuals.
In the study, 2,655 subjects, including 689 DVTFOS patients and 1,966 controls, were recruited. Eighteen SNPs were genotyped in the study. Genetic association analyses were performed at both the single marker and haplotype levels. Bioinformatics analyses were conducted to predict the functional consequences of significant SNPs.
SNP rs2288904 of SLC44A2 was identified as being significantly associated with DVTFOS (P = 0.0003, OR [95%CI] = 1.28[1.12-1.46]). Allelic analyses showed that the G allele of this SNP significantly elevated the risks of DVTFOS, which was replicated in the genotypic association analyses. Moreover, a two-SNP haplotype, including rs2288904, was found to be strongly correlated with the risk of DVTFOS (P = 4.15×10). Widespread effects in the expression quantitative trait loci were identified for rs2288904 in multiple tissues.
In summary, our results provide further supportive evidence of the association of SLC44A2 with the risk of DVTFOS, which also provide clues for understanding the important roles of the SLC44A2 gene in the pathogenesis of DVTFOS and in the development of preventive strategies.
深静脉血栓形成(DVT)是骨科手术后的常见并发症。多条证据表明,遗传因素在骨科手术后 DVT(DVTFOS)的发生中起重要作用。最近的证据表明溶质载体家族 44 成员 2(SLC44A)基因可能与 DVT 的风险有关。本研究旨在探讨 SLC44A2 与汉族人群 DVTFOS 的相关性。
在这项研究中,共纳入了 2655 名受试者,包括 689 名 DVTFOS 患者和 1966 名对照。研究中对 18 个 SNP 进行了基因分型。在单标记和单倍型水平上进行了遗传关联分析。进行了生物信息学分析以预测有意义 SNP 的功能后果。
SLC44A2 的 SNP rs2288904 被鉴定为与 DVTFOS 显著相关(P=0.0003,OR[95%CI]=1.28[1.12-1.46])。等位基因分析表明,该 SNP 的 G 等位基因显著增加了 DVTFOS 的风险,这在基因型关联分析中得到了复制。此外,包括 rs2288904 在内的两个 SNP 单倍型与 DVTFOS 的风险密切相关(P=4.15×10)。在多个组织中鉴定到 rs2288904 的广泛表达数量性状基因座效应。
总之,我们的研究结果为 SLC44A2 与 DVTFOS 风险的相关性提供了进一步的支持证据,这也为理解 SLC44A2 基因在 DVTFOS 发病机制和预防策略发展中的重要作用提供了线索。