Communicated by Nancy B. Spinner
Functional Interaction Between SNPs and Microsatellite in the Transcriptional Regulation of Insulin-Like Growth Factor 1
Article first published online: 8 JUL 2013
© 2013 WILEY PERIODICALS, INC.
Volume 34, Issue 9, pages 1289–1297, September 2013
How to Cite
Chen, H. Y., Huang, W., Leung, V. H. K., Fung, S. L. M., Ma, S. L., Jiang, H. and Tang, N. L. S. (2013), Functional Interaction Between SNPs and Microsatellite in the Transcriptional Regulation of Insulin-Like Growth Factor 1. Hum. Mutat., 34: 1289–1297. doi: 10.1002/humu.22363
Contract grant sponsors: Research Grants Council (RGC), Hong Kong SAR government (CUHK4437/06M); Sir Michael and Lady Kadoorie Funded Research Into Cancer Genetics and Direct Grant, the Chinese University of Hong Kong.
- Issue published online: 14 AUG 2013
- Article first published online: 8 JUL 2013
- Accepted manuscript online: 11 JUN 2013 11:36AM EST
- Manuscript Accepted: 28 MAY 2013
- Manuscript Received: 19 DEC 2012
- Research Grants Council (RGC)
- Hong Kong SAR government. Grant Number: CUHK4437/06M
- Chinese University of Hong Kong
- genetic interaction;
- transcriptional activity
A CA-repeat microsatellite in insulin-like growth factor 1 (IGF1) promoter was associated with interindividual variation of circulating IGF1 level. Previously, we reported that such association was due to variation of haplotype unit in a linkage disequilibrium block composed of microsatellite and single-nucleotide polymorphisms (SNPs), suggesting the presence of an interaction between them. In this study, reporter assays were performed to investigate the regulatory effect and interaction of genetic variants on gene expression. We used an in vitro system to compare the transcriptional activities of haplotypes (rs35767:T>C, the CA-repeat microsatellite, rs5742612:T>C, and rs2288377:T>A) in evolutionarily conserved region of IGF1 promoter. In haplotype C-T-T, a longer microsatellite had a lower transcriptional activity (17.6 ± 2.4-fold for 17 repeats and 8.3 ± 1.1-fold for 21 repeats), whereas in haplotype T-C-A, such trend could not be observed, as the microsatellite with 21 repeats had the highest transcriptional activity (17.5 ± 2.3-fold). Because the microsatellite and SNPs affected the transcriptional activity of each other, there may be an interaction between them in the regulation of IGF1 expression. For the first time, we demonstrated that a noncoding microsatellite polymorphism could act as a functional unit and interact with SNPs in the regulation of transcription in human genome.