Address of Corresponding Author

Horm Res 2006;65 (Suppl. 3):34-40 (DOI: 10.1159/000091504)

  Key Words

• Fetal growth
• Gestational diabetes
• Imprinted genes
• Mitochondrial genes
• Pre-eclampsia

  Abstract

Size at birth is said to be a highly heritable trait, with an estimated 30-70% of the variability a result of genetics. Data from family studies may be confounded, however, by potential interactions between fetal genes and the maternal uterine environment. Overall, the maternal environment tends to restrain fetal growth, and this is most evident in first pregnancies. Restraint of fetal growth appears to be inherited through the maternal line. Potential genetic candidates include the mitochondrial DNA 16189 variant, and common variants of exclusively maternally expressed genes, such as H19, which have been associated with size at birth. Maternal blood glucose levels and blood pressure are also correlated with size at birth, but the degree to which these changes relate to genetic variation in the mother is unclear. Elegant studies in mouse knockout models and rare genetic variants in humans have highlighted the importance of insulin-like growth factor I (IGF-I), IGF-II, insulin and their respective receptors in determining fetal growth. However, data linking common variation in the genes that regulate these proteins and receptors with size at birth are few and inconsistent. Interestingly, common variation in the insulin gene (INS) variable number tandem repeats, which regulates the transcription of insulin and IGF-II, has been associated with size at birth, largely in second and subsequent pregnancies, where maternal restraint is least evident. This suggests that fetal genes, and in particular paternally expressed genes, may have significant effects on fetal growth during pregnancies where maternal restraint of fetal growth is less evident.

Copyright © 2006 S. Karger AG, Basel

  Author Contacts

D.B. Dunger
Department of Paediatrics,University of Cambridge
Addenbrooke's Hospital, Box 116, Level 8, Hills Road
Cambridge CB2 2QQ (UK)
Tel. +44 1223 762 944, Fax +44 1223 336 996, E-Mail dbd25@cam.ac.uk

  Article Information

Published online: April 10, 2006
Number of Print Pages : 7
Number of Figures : 2, Number of Tables : 0, Number of References : 60