Allelic variations in the human growth hormone-1 gene promoter of growth hormone-deficient patients and normal controls.
OBJECTIVE
Isolated growth hormone deficiency (IGHD) type IB is suggested to be more probably due to alterations in the genes directly involved in the hypothalamo-pituitary axis and/or in the specific transcriptional regulation (cis-trans coupling) of the hGH-1 gene than to alterations in the gene itself. In this study we analyzed the hGH-1 gene promoter region for structural alterations and allelic variations.


METHODS
The hGH-1 gene promoter region was analyzed by PCR, cycle sequencing and direct-blotting electrophoresis in a total of 212 individuals including 113 patients with IGHD type IB, 21 unaffected family members and 78 normal controls.


RESULTS
Twenty-two sequence variation sites were identified. Of these, 14% were located around the region of -1075bp, 77% between -550bp and the translational start site (+1bp) and 9% within the first intron. Only one variation site affected a characterized cis-acting element, namely that of NF-1. Importantly, all the variations found in patients were also observed in non-affected family members as well as in normal unrelated controls.


CONCLUSIONS
These findings imply that it is not a single variation within the GH-1 gene promoter, and therefore in the cis-acting elements, which causes IGHD. However, we can not exclude the possibility that combinations of variations might perturb expression. Furthermore, these data illustrate the normal heterogeneity of the GH-1 gene promoter region, a fact that has to be borne in mind whenever transcriptional studies are performed.
Wagner
J K
JK
Department of Pediatrics, University of Bern, Switzerland.
Eblé
A
A
Cogan
J D
JD
Prince
M A
MA
Phillips
J A
JA
Mullis
P E
PE
D000483:Alleles; D001483:Base Sequence; D014644:Genetic Variation / Q000235:genetics*; D019382:Human Growth Hormone / Q000172:deficiency* / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D010375:Pedigree; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012016:Reference Values
D019382:Human Growth Hormone