Sacchi E, Tagliabue L, Scoglio R, Baroncini C, Coppola R, Bernardi F, Mannucci P M
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Maggiore Hospital, Milan, Italy.
Blood Coagul Fibrinolysis. 1996 Mar;7(2):114-7. doi: 10.1097/00001721-199603000-00002.
Genetic factors play a role in determining the variability of plasma factor VII (FVII) levels in healthy individuals. There is also evidence that high serum lipids are associated with high FVII levels in plasma. In the promoter region of the human FVII a DNA polymorphism has been described, originating from a decanucleotide insert present in the less frequent allele. This biallelic system, reflecting the absence (AA) or presence (Aa) of the decanucleotide, can be detected by a DNA enzyme immunoassay of PCR products. We evaluated the association between the polymorphic alleles and the levels of FVII:Ag and FVII:C in 100 healthy individuals and in 19 hypertriglyceridemic individuals. Among healthy individuals, mean FVII:Ag and FVII:C levels of those with the homozygous genotype (A/A; mean FVII:Ag 112%, mean FVII:C 109%) were significantly higher (P < 0.001) than the mean levels of those with the heterozygous genotype (A/a, mean FVII:Ag 80%, mean FVII:C 90%; P < 0.001). Similar genotype-associated differences for FVII:Ag and FVII:C were found in individuals with triglycerides above 250 mg/dl (P < 0.05). FVII:C and FVII:Ag levels were positively related to triglycerides only in individuals without the insert (P < 0.01); there was no significant relationship in those carrying the allele with the insert (A/a; P = 0.43 and 0.08). Our findings of genotype-associated differences in FVII levels and interactions with triglycerides are similar to those obtained with the amino acid dimorphism at position 353 of the factor VII protein.
遗传因素在决定健康个体血浆凝血因子 VII（FVII）水平的变异性方面发挥作用。也有证据表明，高血清脂质与血浆中高 FVII 水平相关。在人类 FVII 的启动子区域，已描述了一种 DNA 多态性，其源于低频等位基因中存在的十核苷酸插入。这种双等位基因系统反映了十核苷酸的缺失（AA）或存在（Aa），可通过对 PCR 产物进行 DNA 酶免疫测定来检测。我们评估了 100 名健康个体和 19 名高甘油三酯血症个体中多态性等位基因与 FVII:Ag 和 FVII:C 水平之间的关联。在健康个体中，纯合基因型（A/A；平均 FVII:Ag 为 112%，平均 FVII:C 为 109%）个体的平均 FVII:Ag 和 FVII:C 水平显著高于（P < 0.001）杂合基因型（A/a，平均 FVII:Ag 为 80%，平均 FVII:C 为 90%；P < 0.001）个体的平均水平。在甘油三酯高于 250 mg/dl 的个体中，也发现了 FVII:Ag 和 FVII:C 类似的基因型相关差异（P < 0.05）。仅在没有插入片段的个体中，FVII:C 和 FVII:Ag 水平与甘油三酯呈正相关（P < 0.01）；在携带插入片段等位基因的个体中（A/a；P = 0.43 和 0.08），没有显著关系。我们关于 FVII 水平的基因型相关差异以及与甘油三酯相互作用的研究结果，与在凝血因子 VII 蛋白 353 位氨基酸二态性研究中获得的结果相似。
