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Current Trends in Endocrinology   Volumes    Volume 6 
The genetic determinants of variations in circulating insulin-like growth factor 1 level and the association with disease predisposition
Holly Y. Chen, Nelson L. S. Tang
Pages: 77 - 90
Number of pages: 14
Current Trends in Endocrinology
Volume 6 

Copyright © 2012 Research Trends. All rights reserved

Insulin-like growth factor 1 (IGF1) plays important roles on tissue growth, energy consumption and cell proliferation through endocrine, paracrine or autocrine mechanisms. There is a significant inter-individual variation of circulating IGF1 level in adults. Strong epidemiological evidences support that a high level of circulating IGF1 (above 75th percentile in the population) is associated with increased cancer risk, while a low level (below 25th percentile in the population) is associated with metabolic diseases such as diabetes mellitus (DM). This review discusses the relationship between variations of circulating IGF1 concentration and susceptibility to diseases, as well as various factors affecting the IGF1 level, particularly the genetic factors. It has been demonstrated that genetic factors contributed to 38% of population variation of IGF1 level by twin studies. Also, genetic polymorphisms in the promoter region are demonstrated to affect the transcriptional activity of IGF1 promoter and thus the expression level of the gene. Recently it was found that the expression of IGF1 was contributed by the whole haplotype consisting of microsatellite and SNPs, rather than either one of them alone as previously thought. The high linkage disequilibrium between the microsatellite and SNPs and the special association pattern between the two polymorphisms imply an interaction between the microsatellite and SNPs in the regulation of IGF1 expression, which will have wider implications for understanding the regulatory mechanisms of genetic polymorphisms in the non-coding region of the genome.
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