Tohoku J. Exp. Med., 2007, 211(1)

Polymorphisms of the Factor VII Gene Associated with the Low Activities of Vitamin K-Dependent Coagulation Factors in One-Month-Old Infants

KOICHI ITO,¹ KENJI GOTO,¹ TOKIO SUGIURA,² KANJI MURAMATSU,³ TOSHIHIRO ANDO,⁴ HIROKO MANIWA,⁵ TAKAO YOKOYAMA,⁵ KOHACHIRO SUGIYAMA⁶ and HAJIME TOGARI¹

¹Department of Pediatrics, Neonatology and Congenital Disorders, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan
²Department of Pediatrics, Toyohashi Municipal Hospital, Nagoya, Japan
³Department of Pediatrics, Nagoya Daini Red Cross Hospital, Nagoya, Japan
⁴Nishimikawa Child and Disabled Person Guidance Center, Okazaki, Japan
⁵Department of Pediatrics, Nishio Municipal Hospital, Nishio, Japan
⁶Sugiyama Children's Clinic, Gifu, Japan

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.

keywords —— Normotest; factor VII polymorphisms; vitamin K; cycling probe; infants

© 2007 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2007, 211, 1-8

Correspondence: Koichi Ito, M.D., 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.

e-mail: k-ito@med.nagoya-cu.ac.jp