title: Polymorphisms of the factor VII gene associated with the low activities of vitamin K-dependent coagulation factors in one-month-old infants.
abstract: 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. 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.
authors.affiliation: Department of Pediatrics, Neonatology and Congenital Disorders, Nagoya City University, Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. k-ito@med.nagoya-cu.ac.jp
authors.forename: Koichi
authors.initials: K
authors.lastname: Ito
authors.forename: Kenji
authors.initials: K
authors.lastname: Goto
authors.forename: Tokio
authors.initials: T
authors.lastname: Sugiura
authors.forename: Kanji
authors.initials: K
authors.lastname: Muramatsu
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Ando
authors.forename: Hiroko
authors.initials: H
authors.lastname: Maniwa
authors.forename: Takao
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Kohachiro
authors.initials: K
authors.lastname: Sugiyama
authors.forename: Hajime
authors.initials: H
authors.lastname: Togari
mesh_terms: D001724:Birth Weight; D001777:Blood Coagulation / Q000502:physiology*; D001779:Blood Coagulation Factors / Q000378:metabolism*; D001780:Blood Coagulation Tests; D001835:Body Weight; D001903:Bottle Feeding; D001942:Breast Feeding; D005167:Factor VII / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D005865:Gestational Age; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D012737:Sex Factors; D014812:Vitamin K / Q000008:administration & dosage / Q000502:physiology*; D014813:Vitamin K Deficiency / Q000150:complications; D006475:Vitamin K Deficiency Bleeding / Q000209:etiology / Q000235:genetics / Q000517:prevention & control
chemical_list: D001779:Blood Coagulation Factors; D014812:Vitamin K; D005167:Factor VII