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Genetic Control of Size at Birth

  • Conference paper
Deciphering Growth

Part of the book series: Research and Perspectives in Endocrine Interactions ((RPEI))

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Summary

Size at birth is a heritable trait: estimates vary between 30% and 70%, but associations may be confounded by interactions with the maternal-uterine environment. Maternal smoking, length of gestation and parity could confound overall estimates of birth weight inheritance. However, the effects of maternal blood pressure, weight gain and glucose levels may be less easy to categorise, as they may reflect genetic factors acting in the mother. First pregnancies are associated with apparent “restraint” of fetal growth. Offspring birth weight in these pregnancies is lower and correlates closely with the mother’s own birth weight, possibly indicating a predominantly maternal inheritance. Candidate genes for maternal transmission of low birth weight include the mitochondrial DNA 16189 variant and exclusively maternally expressed genes such as H19. Offspring birth weight correlations with maternal blood pressure indicate that other maternal genes could influence size at birth in first pregnancies, where risk of pre-eclampsia is greatest. In subsequent pregnancies, gestational diabetes is linked to increased risk of macrosomia, and the impact of higher maternal glucose levels on larger offspring birth weight is demonstrated by a study of families with rare glucokinase gene mutations and in population studies of a common glucokinase gene promoter variant.

Larger birth weight shows a more autosomal mode of inheritance. Potential candidate genes reflect the importance of IGF-I, IGF-2, insulin and their respective receptors in regulating fetal growth, as shown by mouse knockout models and rare genetic variants in human subjects. Identification of common genetic variants associated with size at birth has been less successful. Birth weight association studies with polymorphisms in genes related to IGF-I, insulin and IGF-2 expression have yielded variable results. The common INS VNTR mini-satellite, which regulates INS and IGF2 expression, has been associated with size at birth and is confirmed by parental allele transmission, but has not been replicated in all populations. Animal data indicate the important role of imprinted genes in fetal growth, possibly reflecting the conflict between maternal and paternal influences on size at birth and fetal survival. Although evidence in contemporary human populations remains elusive, preliminary data indicate that such models remain important for future study.

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Authors and Affiliations

  1. University of Cambridge, Addenbrooke’s Hospital, Department of Paediatrics, Box 116 level 8, Hills Road, Cambridge, UK

    D.B. Dunger, C.J. Petry & K.K. Ong

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  1. D.B. Dunger
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  2. C.J. Petry
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  3. K.K. Ong
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Editors and Affiliations

  1. Groupe Hospitalier Cochin-Saint Vincent de Paul-La-Roche Guyon, Hôpital Saint Vincent de Paul INSERM U.561 — Service d’Endocrinologie Pédiatrique, 74 à 82, Av Denfert Rochereau, 75674, Paris, France

    Jean-Claude Carel M.D.

  2. Inserm U584 Faculté de Médecine Necker Enfants Malades, 156, Rue de Vaugirard, 75730, Paris, France

    Paul A. Kelly Ph.D.

  3. Fondation IPSEN Pour la Recherche Thérapeutique, 24, rue Erlanger, 75781, Paris, France

    Yves Christen Ph.D.

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Dunger, D., Petry, C., Ong, K. (2005). Genetic Control of Size at Birth. In: Carel, JC., Kelly, P.A., Christen, Y. (eds) Deciphering Growth. Research and Perspectives in Endocrine Interactions. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-28902-X_3

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