Polymorphisms of the factor VII gene associated with the low activities of vitamin K-dependent coagulation factors in one-month-old infants
Polymorphisms of the factor VII gene associated with the low activities of vitamin K-dependent coagulation factors in one-month-old infants
复制标题
DOI：
10.1620/tjem.211.1
复制
发表时间：
2007-01-01
影响因子：
2.2
通讯作者：
Togari, Hajime
中科院分区：
文献类型：
--
作者：
Ito, Koichi;Goto, Kenji;Togari, Hajime
尽管给予维生素K（VK），一些婴儿显示VK依赖性凝血因子的活性较低，他们可能会发生颅内出血。为了预防婴儿VK缺乏性出血（VKDB），在日本进行口服VK和VK缺乏症筛查试验。对于筛选，使用商业产品Normotest（R）测量VK依赖性凝血因子的总活性。本研究旨在阐明以下遗传和环境因素对1个月大婴儿凝血状态的重要性：因子VII基因的两个多态性，-323P0/10（在启动子区域中在位置-323处的10-bp插入）和R353 Q（在残基353处用谷氨酰胺[Q]替换精氨酸[R]）和性别、年龄、胎龄、出生体重和喂养方案。200名日本婴儿（34.6 +/- 4.0天）进行了筛选VK依赖性凝血活性与Normotest和基因分型的两个多态性。在筛查的受试者中，18名婴儿（9%）携带P10等位基因，26名（13%）携带R353 Q等位基因。多元回归分析表明，10 bp插入（P10）等位基因或Q等位基因与低凝血活性相关。R/Q基因型的凝血活性显著低于R/R基因型，P0/P10基因型的凝血活性显著低于P0/P0基因型。因此，携带P10等位基因或Q等位基因的婴儿显示VK依赖性凝血因子的活性较低。这些婴儿可能有较高的风险VKDB表现。
Despite administration of vitamin K (VK), some infants show lower activity of VK-dependent coagulation factors and they could develop intracranial hemorrhage. For preventing VK deficiency bleeding (VKDB) in infants, oral administration of VK and a screening test for VK deficiency are carried out in Japan. For the screening, the total activity of VK-dependent coagulation factors is measured using a commercial product, Normotest (R). This study was undertaken to clarify the importance of the following genetic and environmental factors on the coagulation status in one-month-old infants: two polymorphisms in the factor VII gene, -323P0/10 (a 10-bp insertion in the promoter region at position -323) and R353Q (the replacement of arginine [R] with glutamine [Q] at residue 353) and sex, age, gestational age, birth weight, and feeding regimen. Two hundred Japanese infants (34.6 +/- 4.0 days old) were screened for VK-dependent coagulation activity with Normotest and were genotyped for the two polymorphisms. Among the subjects screened, 18 infants (9%) carried the P10 allele and 26 (13%) carried the R353Q allele. Multiple regression analysis showed that the 10-bp inserted (P10) allele or the Q allele was associated with the lower coagulation activities. The coagulation activities for the R/Q genotype were significantly lower than those for the R/R genotype and those for the P0/P10 genotype were significantly lower than those for the P0/P0 genotype. Therefore, infants who carry the P10 allele or the Q allele show lower activity of VK-dependent coagulation factors. These infants may have a higher risk of VKDB manifestation.