HGH - Human Growth Hormone (GH1) Gene ExpressionHoran M, Millar DS, Hedderich J, Lewis G, Newsway V, Mo N, Fryklund L, Procter AM, Krawczak M, Cooper DN. Institute of Medical Genetics, University of Wales College of Medicine, Cardiff, UK. The proximal promoter region of the human pituitary expressed growth hormone (GH1) gene is highly polymorphic, containing at least 15 single nucleotide polymorphisms (SNPs). This variation is manifest in 40 different haplotypes, the high diversity being explicable in terms of gene conversion, recurrent mutation, and selection. Functional analysis showed that 12 haplotypes were associated with a significantly reduced level of reporter gene expression whereas 10 haplotypes were associated with a significantly increased level. The former tend to be more prevalent in the general population than the latter (p<0.01), possibly as a consequence of selection. Although individual SNPs contributed to promoter strength in a highly interactive and non-additive fashion, haplotype partitioning was successful in identifying six SNPs as major determinants of GH1 gene expression. The prediction and functional testing of hitherto unobserved super-maximal and sub-minimal promoter haplotypes was then used to test the efficacy of the haplotype partitioning approach. Electrophoretic mobility shift assays demonstrated that five SNP sites exhibit allele-specific protein binding. An association was noted between adult height and the mean in vitro expression value corresponding to an individual's GH1 promoter haplotype combination (p=0.028) although only 3.3% of the variance of adult height was found to be explicable by reference to this parameter. Three additional SNPs, identified within sites I and II of the upstream locus control region (LCR), were ascribed to three distinct LCR haplotypes. A series of LCR-GH1 proximal promoter constructs were used to demonstrate that 1) the LCR enhanced proximal promoter activity by up to 2.8-fold depending upon proximal promoter haplotype, and that 2) the activity of a given proximal promoter haplotype was also differentially enhanced by different LCR haplotypes. The genetic basis of inter-individual differences in GH1 gene expression thus appears to be extremely complex. Copyright 2003 Wiley-Liss, Inc. Publication Types:
Click here to Buy HGH Human Growth Hormone
|
Terms of Use - Privacy
Policy
Disclaimer: Content on this site is
for reference purposes and is not intended to substitute for
advice given by a physician, pharmacist, or other licensed
health-care professional. You should not use this information as
self-diagnosis or for treating a health problem or disease.
Links and content located on other sites is not our
responsibility. Do your own due diligence before purchasing any
product. Contact your health-care provider immediately if you
suspect that you have a medical problem. Information and
statements regarding dietary supplements have not been evaluated
by the Food and Drug Administration and are not intended to
diagnose, treat, cure, or prevent any disease or health
condition.