title: Functional interaction between SNPs and microsatellite in the transcriptional regulation of insulin-like growth factor 1.
abstract: 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.
authors.affiliation: Department of Chemical Pathology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
authors.forename: Holly Y
authors.initials: HY
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Vincent H K
authors.initials: VH
authors.lastname: Leung
authors.forename: Simon L M
authors.initials: SL
authors.lastname: Fung
authors.forename: Suk Ling
authors.initials: SL
authors.lastname: Ma
authors.forename: Hongling
authors.initials: H
authors.lastname: Jiang
authors.forename: Nelson L S
authors.initials: NL
authors.lastname: Tang
mesh_terms: D001483:Base Sequence; D005786:Gene Expression Regulation; D014644:Genetic Variation; D015894:Genome, Human; D006239:Haplotypes; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism*; D015810:Linkage Disequilibrium; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
chemical_list: C583557:IGF1 protein, human; D007334:Insulin-Like Growth Factor I
keywords: IGF1; SNP; genetic interaction; promoter; transcriptional activity