Plasma phenotypes of protein S Lys196Glu and protein C Lys193del variants prevalent among young Japanese women
Plasma phenotypes of protein S Lys196Glu and protein C Lys193del variants prevalent among young Japanese women
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DOI：
10.1097/mbc.0000000000000854
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发表时间：
2019-12-01
影响因子：
1.1
通讯作者：
Tsuda, Hiroko
中科院分区：
文献类型：
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作者：
Noguchi, Kenta;Nakazono, Eri;Tsuda, Hiroko
蛋白S Tokushima （p.Lys196Glu）和两个蛋白C基因变体（p.l arg189trp, p.Lys193del）分别在日本和中国人群中是遗传性血栓性疾病；然而，由于II型缺乏表型，通过血浆分析诊断是困难的。在日本年轻女性（n = 231）中检测了三种基因变异基因型。血浆总蛋白S活性和总蛋白S抗原水平采用总蛋白S测定系统，蛋白C和蛋白S活性采用血块法测定，蛋白C和游离蛋白S抗原水平采用乳胶凝集法测定。蛋白质S Tokushima （p.Lys196Glu）和蛋白质C p.Lys193del变体在参与者中普遍存在，等位基因频率分别为1.08和0.86%，而蛋白质C p.g arg189trp变体的携带者未被发现。血浆中总蛋白S活性降低，总蛋白S抗原水平正常，表明德岛杂合子II型蛋白S缺乏；而蛋白C p.Lys193del杂合子的蛋白C活性在参考区间内，蛋白C抗原水平升高。我们比较了总蛋白S活性/总蛋白S抗原比与基于凝块的蛋白S活性/游离蛋白S抗原比对蛋白S德岛杂合子的诊断准确性，发现只有前者才能达到100%的敏感性和100%的特异性。蛋白S Tokushima和蛋白C p.Lys193del在日本年轻女性中普遍存在，使用总蛋白S测定系统进行血浆分析比基于凝块的蛋白S活性/游离蛋白S抗原比诊断蛋白S Tokushima携带者更准确。
Protein S Tokushima (p.Lys196Glu) and two protein C gene variants (p.Arg189Trp, p.Lys193del) are hereditary thrombophilia in Japanese and Chinese populations, respectively; however, their diagnosis by plasma analyses is difficult because of the type II deficiency phenotype. Three gene variant genotypes were examined in young Japanese women (n = 231). Plasma total protein S activity and total protein S antigen levels were measured using a total protein S assay system, protein C and protein S activities by clot-based methods, and protein C and free protein S antigen levels by latex agglutination methods. protein S Tokushima (p.Lys196Glu) and protein C p.Lys193del variants were prevalent among participants with allele frequencies of 1.08 and 0.86%, respectively, whereas any carrier of protein C p.Arg189Trp variant was not identified. The plasma phenotype of the type II deficiency of protein S Tokushima heterozygotes was demonstrated by decreased total protein S activity with a normal total protein S antigen level; however, the protein C activities of protein C p.Lys193del heterozygotes were within reference intervals, whereas their protein C antigen levels were elevated. We compared the diagnostic accuracy of the total protein S activity/total protein S antigen ratio for identifying protein S Tokushima heterozygotes with that of the clot-based protein S activity/free protein S antigen ratio and found that sensitivity and specificity of 100% each was only achieved by the former. Protein S Tokushima and protein C p.Lys193del are prevalent among young Japanese women, and a plasma analysis using the total protein S assay system is more accurate than the clot-based protein S activity/free protein S antigen ratio for diagnosing protein S Tokushima carriers.