Document Detail

Genetic variation at the growth hormone (GH1) and growth hormone receptor (GHR) loci as a risk factor for hypertension and stroke.
MedLine Citation:
PMID:  16572267     Owner:  NLM     Status:  MEDLINE    
An increased prevalence of both hypertension and cerebrovascular stroke is apparent in growth hormone (GH) deficiency whilst hypertension is a frequent complication in acromegaly. This has suggested a possible link between GH, stature and arterial function. Since the risk of both hypertension and stroke also appears to be inversely correlated with adult height, we have instigated an exploratory study to assess whether inter-individual variation in the genes encoding human growth hormone (GH1) and the GH receptor (GHR) might be associated with an increased risk of hypertension and stroke. GH1 promoter haplotypes were found to differ significantly not only between hypertensive patients (n = 111) and controls (n = 121) but also between stroke patients (n = 155) and controls (n = 158). Intriguingly, the association between GH1 promoter haplotype and risk of hypertension was much greater in females than in males. An inverse correlation between height and central systolic blood pressure was apparent in both hypertensive patients and normal controls but was much stronger in individuals carrying at least one GH1 promoter risk haplotype. The GH1 genotype therefore constitutes a risk factor for hypertension that interacts with stature. A strong association was found between the presence of at least one GH1 risk haplotype and a family history of stroke at an early age (odds ratio: 9.07, 95% confidence interval: 1.14-72.22). Three novel GH variants (Arg16His, Phe176Cys, Cys189Arg) were identified during the course of this study. Although two exhibited markedly reduced biological activity in vitro, their clinical significance remains unclear. No association was found between GHR genotype and either hypertension or stroke, nor was any interaction noted between GHR and GH1 genotypes in terms of a disease association. However, an association between GHRd3 genotype and hypertension was observed among stroke patients, particularly females. Elevated HDL was found to be a risk factor for hypertension in individuals lacking a copy of the GHRd3 allele. Weak associations with GHR genotype were also noted for peripheral systolic and diastolic blood pressure in hypertensive patients. Although the underlying mechanisms are still unclear, our findings are consistent with a complex relationship between height, hypertension, GH1 promoter haplotype, GHR polymorphism and the risk of stroke.
Martin Horan; Vicky Newsway; Yasmin; Mark D Lewis; Tammy E Easter; D Aled Rees; Arti Mahto; David S Millar; Annie M Procter; Maurice F Scanlon; Ian B Wilkinson; Ian P Hall; Amanda Wheatley; John Blakey; Philip M W Bath; John R Cockcroft; Michael Krawczak; David N Cooper
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-03-30
Journal Detail:
Title:  Human genetics     Volume:  119     ISSN:  0340-6717     ISO Abbreviation:  Hum. Genet.     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-05-03     Completed Date:  2006-12-01     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  7613873     Medline TA:  Hum Genet     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  527-40     Citation Subset:  IM    
Institute of Medical Genetics, Cardiff University, Heath Park, CF14 4XN, Cardiff, UK.
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MeSH Terms
Aged, 80 and over
Body Height / genetics
Genetic Markers
Genetic Variation*
Growth Hormone / genetics*
Hypertension / genetics*
Middle Aged
Pilot Projects
Receptors, Somatotropin / genetics*
Risk Factors
Stroke / genetics*
Reg. No./Substance:
0/Genetic Markers; 0/Receptors, Somatotropin; 9002-72-6/Growth Hormone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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