Characterisation of a functional intronic polymorphism in the human growth hormone (GH1) gene

Millar, David Stuart, Horan, Martin Patrick, Chuzhanova, Nadia A. and Cooper, David Neil ORCID: https://orcid.org/0000-0002-8943-8484 2010. Characterisation of a functional intronic polymorphism in the human growth hormone (GH1) gene. Human Genomics 4 (5) , pp. 289-301.

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Abstract

The +1169A allele of the A/T single nucleotide polymorphism (SNP; rs2665802), located within intron 4 of the human growth hormone 1 ( GH1 ) gene, has been associated with reduced levels of circulating GH and insulin-like growth factor 1, a reduced risk of colorectal cancer and a predisposition to osteoporosis. Whether this intronic SNP is itself the functional polymorphism responsible for exerting a direct effect on GH1 gene expression, however, or whether it is instead in linkage disequilibrium with the functional SNP, has been an open question. The evolutionary conservation of the +1169T allele (and the surrounding intronic sequence) in the bovine genome, as well as in primate genomes, is, however, suggestive of its functionality. Although a potential alternative splice site spans the location of the +1169 SNP, polymerase chain reaction-based assays failed to yield any evidence for alternative splicing associated with either allele. To determine whether the +1169 SNP, in different allelic combinations with SNPs at -278 (G/T), -57 (T/G) and +2103 (C/T), exerts a direct effect on gene expression and/or GH secretion, we performed a series of transfections of various GH1 haplotype-expressing constructs into rat GC (somatotroph) cells. The results obtained provided evidence to support the contention that the +1169A allele contributes directly to the observed reduction in both GH1 gene expression and GH secretion. Part of the apparent influence of the +1169A-bearing allele on GH1 gene expression and GH secretion may still, however, be attributable to alleles of additional SNPs in cis to +1169A and located within either the promoter or the 3'-flanking region.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Cardiff Catalysis Institute (CCI)
Subjects:	Q Science > QH Natural history > QH426 Genetics R Medicine > R Medicine (General)
Uncontrolled Keywords:	growth hormone (GH1) gene; gene expression; protein secretion; intronic functional polymorphism; alternative splicing
Publisher:	Henry Stewart Publications
ISSN:	1479-7364
Last Modified:	06 May 2023 01:14
URI:	https://orca.cardiff.ac.uk/id/eprint/18704

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