Research Collaborations in Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Division of Hematology, Department of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
Research Collaborations in Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Division of Hematology, Department of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
Thromb Res. 2019 Jun;178:7-11. doi: 10.1016/j.thromres.2019.03.013. Epub 2019 Mar 21.
In contrast to Caucasians, hereditary anticoagulant deficiencies are more common in Asians and mutations are heterogeneous among different countries. This study aimed to determine the prevalence and genetic basis of protein C and protein S deficiencies in Thai population.
Healthy volunteers were tested for protein C activity and free protein S antigen. Subjects with low values were requested for repeated testing and exclusion of acquired causes. Cases with persistently low levels were assayed for respective gene mutations using direct sequencing and multiplex ligation-dependent probe amplification (MPLA) when PROS1 point mutation was undetectable.
For protein C activities (N = 5234), the values of men were lower than those of post-menopausal women (P < 0.001). In 17 of 18 subjects, there were 7 types of PROC mutations, 64.7% of which were p.R189W and 2 were previously unreported. Protein S levels (N = 5242) were highest in men, followed by post-menopausal and pre-menopausal women, respectively (P < 0.001). The repeatedly low protein S was mostly in female (88.2%). Among 29 subjects with protein S below the sex-specific 2.5 percentile cut-points, 4 types of mutations were found in 5 subjects (17.2%) with one previously unreported mutation. Free protein S levels were below 30 U/ml in all cases with mutations. The estimated prevalence of PROC and PROS1 mutations in Thai population was 0.69% and 0.22%, respectively.
PROC mutations, especially p.R189W, are common in Thais. However, mildly depressed protein S levels were frequently found in women with undetectable PROS1 mutation.
与白种人相比，遗传性抗凝因子缺乏症在亚洲人群中更为常见，且突变在不同国家之间存在异质性。本研究旨在确定泰国人群中蛋白 C 和蛋白 S 缺乏症的流行率和遗传基础。
健康志愿者检测蛋白 C 活性和游离蛋白 S 抗原。低值者要求重复检测并排除获得性原因。对于持续低值者，当 PROS1 点突变不可检测时，采用直接测序和多重连接依赖性探针扩增（MPLA）检测相应基因突变。
对于蛋白 C 活性（N=5234），男性值低于绝经后女性（P<0.001）。在 18 例中有 17 例存在 PROC 突变，其中 64.7%为 p.R189W，有 2 例为之前未报道过的突变。蛋白 S 水平（N=5242）以男性最高，其次是绝经后和绝经前女性（P<0.001）。反复低值蛋白 S 主要见于女性（88.2%）。在 29 例蛋白 S 低于性别特异性 2.5%位数切点的患者中，5 例（17.2%）发现 4 种突变，其中 1 种为之前未报道过的突变。所有突变患者的游离蛋白 S 水平均低于 30 U/ml。泰国人群 PROC 和 PROS1 突变的估计患病率分别为 0.69%和 0.22%。
PROC 突变，特别是 p.R189W，在泰国人群中很常见。然而，在 PROS1 突变不可检测的女性中，常发现轻度降低的蛋白 S 水平。
