Bernardi F, Arcieri P, Bertina R M, Chiarotti F, Corral J, Pinotti M, Prydz H, Samama M, Sandset P M, Strom R, Garcia V V, Mariani G
Dipartimento di Biochimica e Biologia Molecolare, Università degli Studi di Ferrara, Italy.
Arterioscler Thromb Vasc Biol. 1997 Nov;17(11):2548-53. doi: 10.1161/01.atv.17.11.2548.
The relationship between coagulation factor VII (FVII) levels in plasma and FVII genotypes, determined by three polymorphisms (5'F7, IVS7, and 353R/Q), were studied in 500 control subjects enrolled in European multicenter study. The selection of particular FVII genotypes and the analysis of variance clearly indicated the independent contribution of a single 5'F7 insertion (A2) or 353Q (M2) allele to lowering plasma levels of activated FVII (FVIIa) (by a mean 25%). The M2 allele alone was found to make a major contribution to the genetically determined component of the FVIIa levels. Genotypes associated with low FVII levels were significantly rarer in the northern part of Europe (Oslo) than in the southern part (Rome, Murcia). The contribution made by the FVII genotype to the total variance of FVIIa levels was higher (30%) than that made to either FVII activity (25%) or FVII antigen (12%). Subjects with different FVII genotypes showed up to fivefold differences in mean FVIIa values, thus allowing attribution of a substantial part of the considerable interindividual variation to genetic variation, which may be of assistance in the interpretation of FVIIa levels on an individual basis. When FVII levels were adjusted by age and by triglyceride levels, the contribution of FVII genotypes to the FVII phenotypic variance was virtually unchanged. Taken together, these data indicate that in healthy control subjects the FVII genotype is a major predictor of plasma FVIIa levels and would support further study on the role of FVII genetic components in the development of cardiovascular disease.
在一项欧洲多中心研究纳入的500名对照受试者中，研究了血浆中凝血因子VII（FVII）水平与由三种多态性（5'F7、IVS7和353R/Q）所确定的FVII基因型之间的关系。特定FVII基因型的选择和方差分析清楚地表明，单个5'F7插入（A2）或353Q（M2）等位基因对降低活化FVII（FVIIa）的血浆水平有独立作用（平均降低25%）。仅M2等位基因就被发现对FVIIa水平的遗传决定成分有主要贡献。与低FVII水平相关的基因型在欧洲北部（奥斯陆）比在南部（罗马、穆尔西亚）明显少见。FVII基因型对FVIIa水平总方差的贡献高于对FVII活性（25%）或FVII抗原（12%）的贡献。具有不同FVII基因型的受试者在平均FVIIa值上显示出高达五倍的差异，因此可以将个体间相当大的变异的很大一部分归因于基因变异，这可能有助于在个体基础上解释FVIIa水平。当根据年龄和甘油三酯水平对FVII水平进行调整时，FVII基因型对FVII表型方差的贡献几乎不变。综上所述，这些数据表明，在健康对照受试者中，FVII基因型是血浆FVIIa水平的主要预测指标，并支持进一步研究FVII基因成分在心血管疾病发生中的作用。
