凝血因子V（FV）基因ASP79HIS多态性可调节FV血浆水平，并在存在FV莱顿突变的情况下影响活化蛋白C抵抗表型。

The factor V (FV) gene ASP79HIS polymorphism modulates FV plasma levels and affects the activated protein C resistance phenotype in presence of the FV Leiden mutation.

作者信息

Bossone Anna, Cappucci Filomena, D'Andrea Giovanna, Brancaccio Vincenzo, Cibelli Giuseppe, Iannaccone Luigi, Grandone Elvira, Margaglione Maurizio

机构信息

Unità di Aterosclerosi e Trombosi, IRCCS Casa Sollievo della Sofferenza, viale Cappuccini, San Giovanni Rotondo, 71013 Foggia, Italy.

出版信息

Haematologica. 2003 Mar;88(3):286-9.

PMID:12651267

Abstract

BACKGROUND AND OBJECTIVES

In carriers of the factor V (FV) Leiden mutation, different trans-acting gene variants (HR2 haplotype and FV Cambridge mutation) affect activated protein C (APC) sensitivity. Among a series of FV gene variants characterized, the Asp79His polymorphism appeared to be a good candidate for the modulation of FV activity.

DESIGN AND METHODS

In a group of 150 apparently healthy subjects without the FV Leiden mutation and in 55 apparently healthy subjects with mutation, genotypes of the Asp79His polymorphism and of the HR haplotype were characterized and plasma levels of FV coagulant activity and APC ratios evaluated.

RESULTS

In the group without the FV Leiden mutation, 16 subjects (10.7%) carried the His 79 allele and 15 subjects (10.0%) the HR2 haplotype. Two of them carried both gene variants. As compared to FV activity levels in non-carriers (106.4+18.5%), values were lower in subjects with the His79 allele (95.2+25.2%; p=0.025) and in those with the HR2 haplotype (93.7+16.2%; p =0.007). FV activity levels were further reduced in carriers of both FV gene variants (78.7+3.3%; p =0.009). APC values were similar among individuals carrying different FV genotypes. In the group with the FV Leiden mutation, APC ratios were lower in subjects carrying the His 79 allele (0.63; p =0.008) or the HR2 haplotype (0.63; p =0.026) than in subjects without (0.69) reflecting FV activity values.

INTERPRETATION AND CONCLUSIONS

Present data suggest that carriership of the His79 allele modulate plasma levels of FV coagulant activity and, in subjects carrying the FV Leiden mutation, affects APC sensitivity.

摘要

背景与目的

在因子V（FV）Leiden突变携带者中，不同的反式作用基因变异（HR2单倍型和FV剑桥突变）会影响活化蛋白C（APC）敏感性。在一系列已鉴定的FV基因变异中，Asp79His多态性似乎是调节FV活性的一个良好候选因素。

设计与方法

在一组150名无FV Leiden突变的明显健康受试者和55名有该突变的明显健康受试者中，对Asp79His多态性和HR单倍型的基因型进行了鉴定，并评估了FV凝血活性的血浆水平和APC比率。

结果

在无FV Leiden突变的组中，16名受试者（10.7%）携带His 79等位基因，15名受试者（10.0%）携带HR2单倍型。其中两名受试者同时携带这两种基因变异。与非携带者的FV活性水平（106.4 + 18.5%）相比，携带His79等位基因的受试者（95.2 + 25.2%；p = 0.025）和携带HR2单倍型的受试者（93.7 + 16.2%；p = 0.007）的值较低。同时携带两种FV基因变异的携带者中FV活性水平进一步降低（78.7 + 3.3%；p = 0.009）。携带不同FV基因型的个体之间APC值相似。在有FV Leiden突变的组中，携带His 79等位基因（0.63；p = 0.008）或HR2单倍型（0.63；p = 0.026）的受试者的APC比率低于无该突变的受试者（0.69），反映了FV活性值。