Semin Thromb Hemost 2005; 31: 334-345 DOI: 10.1055/s-2005-872441
Copyright © 2005 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.
Genetic Factors in Fetal Growth Restriction and Miscarriage
Hideto Yamada1,2, Fumihiro Sata3, Yasuaki Saijo3, Reiko Kishi3, Hisanori Minakami2
1 Associate Professor, Hokkaido University Graduate School of Medicine, Sapporo, Japan 2 Department of Obstetrics and Gynecology, Hokkaido University Graduate School of Medicine, Sapporo, Japan 3 Department of Public Heath, Hokkaido University Graduate School of Medicine, Sapporo, Japan

ABSTRACT

Recently, several investigations concerning disadvantageous genetic factors in human reproduction have progressed. Inherited thrombophilia, such as factor V Leiden, prothrombin, and methylenetetrahydrofolate reductase mutations; gene polymorphisms of detoxification enzyme (CYP1A1); growth factors (insulin-like growth factor-I); and hormones such as angiotensinogen and CYP17 are involved in the pathogenesis of fetal growth restriction. The inherited thrombophilia, gene polymorphisms of coagulation and anticoagulation factor such as thrombomodulin, endothelial protein C receptor, plasminogen activator inhibitor 1, and factor XIII; human lymphocyte antigen (HLA-G); detoxification enzymes (glutathione-S-transferase M1); cytokines such as interleukin (IL) -1 and IL-6; hormones (CYP17); vasodilators (nitric oxide synthase 3); and vitamins (transcobalamin) are involved in the pathogenesis of sporadic and recurrent miscarriage. It is likely that a gene polymorphism or mutation susceptible to reproductive failure has a beneficial effect on the process of human reproduction with or without the environmental interaction. The factor V Leiden mutation has genetic advantages that are believed to be an improved implantation rate in in vitro fertilization and a reduction of maternal intrapartum blood loss. It has also been demonstrated that the CYP17 A2 allele has bidirectional effects on human reproduction, including increases in susceptibility to recurrent miscarriage and fetal growth enhancement.

KEYWORDS

Abortion - fetal growth restriction - genetic polymorphism - miscarriage