Protein S Deficiency and the Risk of Venous Thromboembolism in the Han Chinese Population.
Protein S Deficiency and the Risk of Venous Thromboembolism in the Han Chinese Population.
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DOI：
10.3389/fcvm.2021.796755
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发表时间：
2021
影响因子：
3.6
通讯作者：
中科院分区：
文献类型：
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据报道，在欧洲和东南亚人群中，血浆中抗凝血辅助因子蛋白S和PROS1突变水平会增加血栓栓塞的风险，但在基于人群的研究中，这一关系尚未在汉族人群中得到证实。因此，我们对静脉血栓栓塞患者的这种关系进行了病例对照研究，并探讨了导致低蛋白S缺乏的遗传因素。在603例连续招募的静脉血栓栓塞患者中，51例（8.5%）被证实缺乏游离蛋白S抗原（低于38.6 U/dl），其中30例通过直接测序确定有致病突变。相比之下，584例健康对照中有6例（1.0%）的游离抗原水平较低，其中4例（0.7%）的直接测序证实了致病基因突变。在调整年龄和性别后，基于游离蛋白S检测的蛋白S缺乏个体发生静脉血栓栓塞的优势比为8.1 （95% CI = 3.6-19.9, P < 0.001）。基因测序在34名参与者中发现了24种不同的杂合突变，其中13种是新发现的。在我们的研究队列中，34个突变中有17个（50%）发生在外显子12和13上，这表明LGR2结构域是该蛋白的热点突变区域。这些发现有利于蛋白S检测在血栓病分子诊断中的临床应用。
Plasma levels of the anticoagulant cofactor protein S and PROS1 mutation are reported to impart increased risk of thromboembolism in European and south east Asian populations, but the relationship is not yet documented in Han Chinese in population-based study. Therefore, we undertook a case-control study of this relationship among patients with venous thromboembolism, and probed the genetic factors contributing to low protein S deficiency. Among the 603 consecutively recruited venous thromboembolism patients, 51 (8.5%) proved to be deficient in free protein S antigen (lower than 38.6 U/dl), among whom 30 cases were identified to have a causative mutation by direct sequencing. In contrast, six cases (1.0%) of the 584 healthy controls had low free antigen levels, among whom direct sequencing confirmed disease-causing gene mutations in four controls (0.7%). After adjusting for age and gender, the odds ratio of developing venous thromboembolism in individuals with protein S deficiency based on free protein S tests was 8.1 (95% CI = 3.6–19.9, P < 0.001). Gene sequencing yielded 24 different heterozygous mutations in the 34 participants, of which 13 were newly described. 17 (50%) of the 34 mutations in our study cohort occurred in exons 12 and 13, indicating the LGR2 domain to be a hotspot mutation region for the protein. These findings are conducive to the clinical application of protein S assays for the molecular diagnosis of thrombophilia.