Activated protein C resistance as an additional risk factor for thrombosis in protein C-deficient families.
Activated protein C resistance as an additional risk factor for thrombosis in protein C-deficient families.
复制标题
活化的蛋白 C 抵抗是蛋白 C 缺乏家族中血栓形成的另一个危险因素。
作者：
B. Koeleman;P. Reitsma;C. Allaart;R. Bertina
杂合蛋白 C 缺乏与血栓形成风险增加相关。这种关联仅限于少数蛋白 C 缺陷家族，这些家族被定义为临床显性蛋白 C 缺陷。相比之下，在临床隐性蛋白 C 缺陷家族中，只有纯合家族成员受到（严重）影响。家庭之间血栓形成风险差异的一种可能解释可能是存在第二个遗传风险因素。第二个危险因素的一个很好的候选者是最近发现的对活化蛋白 C (APC) 的耐药性。 APC 抵抗与 FV 基因 (FV Leiden) 突变相关，是血栓形成的常见且强烈的危险因素。我们在此表明，有症状的蛋白 C 缺陷先证者中 FV Leiden 突变的患病率很高（19%）。在6个临床显性蛋白C缺陷家族中，研究了FV Leiden突变和蛋白C基因突变的分离。 73% 的家族成员同时具有 C 蛋白基因突变和 FV Leiden 突变，曾经历过血栓形成。相比之下，具有 Protein C 基因突变或 FV Leiden 突变的家庭成员中分别有 31% 和 13% 经历过血栓形成。此外，两个基因座连锁分析的结果支持FV基因和蛋白C基因是导致血栓形成倾向的两个性状基因座的假设。这些结果表明，与单一缺陷的相关携带者相比，两种基因缺陷的携带者血栓形成的风险增加。
Heterozygous protein C deficiency is associated with an increased risk for thrombosis. This association is restricted to a minority of protein C-deficient families, which have been defined as clinically dominant protein C-deficient. In contrast, in the clinically recessive protein C-deficient families, only the homozygous family members are (severely) affected. One possible explanation for this difference in thrombotic risk between families may be the presence of a second hereditary risk factor. A good candidate for this second risk factor is the recently identified resistance to activated protein C (APC). APC resistance, which is associated with a mutation in the FV gene (FV Leiden), is a common and strong risk factor for thrombosis. We show here that the prevalence of the FV Leiden mutation is high among symptomatic protein C-deficient probands (19%). In 6 clinically dominant protein C-deficient families, the segregation of the FV Leiden mutation and the protein C gene mutation was studied. A thrombotic episode had been experienced by 73% of the family members having both the protein C gene mutation and the FV Leiden mutation. In contrast, respectively, 31% and 13% of the family members having either the protein C gene mutation or the FV Leiden mutation had experienced a thrombotic episode. Moreover, the result of a two locus linkage analysis support the assumption that the FV gene and the protein C gene are the two trait loci responsible for the thrombophilia. These results indicate that carriers of both gene defects have an increased risk for thrombosis compared with related carriers of the single defect.
DOI：
10.1161/01.atv.12.2.135
发表时间：
1992-02-01
期刊：
ARTERIOSCLEROSIS AND THROMBOSIS
影响因子：
--
作者：
ESMON, CT
通讯作者：
ESMON, CT
影响因子：
158.5
作者：
MILETICH, J;SHERMAN, L;BROZE, G
通讯作者：
BROZE, G