Human Genetics

, Volume 122, Issue 1, pp 1–21 | Cite as

Molecular genetics of human growth hormone, insulin-like growth factors and their pathways in common disease

  • Santiago RodriguezEmail author
  • Tom R. Gaunt
  • Ian N. M. Day


The human growth hormone gene (GH1) and the insulin-like growth factor 1 and 2 genes (IGF1 and IGF2) encode the central elements of a key pathway influencing growth in humans. This “growth pathway” also includes transcription factors, agonists, antagonists, receptors, binding proteins, and endocrine factors that constitute an intrincate network of feedback loops. GH1 is evolutionarily coupled with other genes in linkage disequilibrium in 17q24.2, and the same applies to IGF2 in 11p15.5. In contrast, IGF1 in 12q22-24.1 is not in strong linkage disequilibrium with neighbouring genes. Knowledge of the functional architecture of these regions is important for the understanding of the combined evolution and function of GH1, IGF2 and IGF1 in relation to complex diseases. A number of mutations accounting for rare Mendelian disorders have been described in GH-IGF elements. The constellation of genes in this key pathway contains potential candidates in a number of complex diseases, including growth disorders, metabolic syndrome, diabetes (notably IGF2BP2) cardiovascular disease, and central nervous system diseases, and in longevity, aging and cancer. We review these genes and their associations with disease phenotypes, with special attention to metabolic risk traits.


Growth Hormone Tyrosine Hydroxylase Growth Hormone Deficiency Locus Control Region Mechano Growth Factor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We thank three anonymous reviewers for their helpful comments. Work in our laboratory has been funded by UK MRC and British Heart Foundation, also by University of Bristol, UK. TRG is funded by a BHF (British Heart Foundation) Intermediate Fellowship (FS/05/065/19497).

Supplementary material


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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Santiago Rodriguez
    • 1
    Email author
  • Tom R. Gaunt
    • 1
  • Ian N. M. Day
    • 1
  1. 1.Bristol Genetic Epidemiology Laboratories (BGEL) and MRC Centre for Causal Analyses in Translational Epidemiology (CAiTE), Department of Social MedicineUniversity of BristolBristolUK

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