| Chromosome 2p shows significant linkage to antihypertensive response in the British Genetics of Hypertension Study. | |
| | |
MedLine Citation:
|
PMID: 16391175 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
There is a lack of consistently linked loci influencing blood pressure and hypertension status, and this may be because of genetic or phenotypic heterogeneity. We hypothesize that stratification of subjects by response to antihypertensive drug groups could be used to stringently define subsets that will have reduced genetic and etiologic heterogeneity, by partitioning contrasting mechanisms of hypertension and, thus, enhancing gene finding. We investigated the British Genetics of Hypertension Study population, which is composed of 2142 severely hypertensive white affected sibling pairs. Nonresponse to antihypertensive therapy was defined as an on-treatment blood pressure of >140/90 mm Hg or a difference between prediagnosis and on-treatment blood pressure of <20 mm Hg. Of the nonresponders, there were 89 sibling pairs (AB) who were both on antihypertensive therapy that inhibit the renin-angiotensin system (angiotensin-converting enzyme inhibitors, angiotensin II type-1 receptor blockers, or beta-blockers), and 76 sibling pairs (CD) who were both on drugs that do not (calcium channel blockers or diuretics). Nonparametric linkage analysis carried out using markers from a 10-cM genome scan and additional "grid tightening" markers showed significant linkage in the AB group on chromosome 2p (logarithm of odds=4.84 at 90.68 Kosambi cM) and suggestive linkage for the CD group on chromosome 10q (logarithm of odds=2.83 at 125.96 Kosambi cM). The AB linkage locus attained genomewide significance after simulation using 10,000 replicates (P=0.005). This locus may contain a gene for the salt-sensitive form of hypertension and/or a pharmacogenetic locus affecting drug response. We have demonstrated for the first time identification of a significant locus by partitioning different pathways of hypertension using drug response. |
| | |
Authors:
|
Sandosh Padmanabhan; Chris Wallace; Patricia B Munroe; Richard Dobson; Morris Brown; Nilesh Samani; David Clayton; Martin Farrall; John Webster; Mark Lathrop; Mark Caulfield; Anna F Dominiczak; John M Connell |
Related Documents
:
|
16788695 - 24-h ambulatory blood pressure is linked to chromosome 18q21-22 and genetic variation o... 19451835 - Cyp1a2 genotype modifies the association between coffee intake and the risk of hyperten... 1358065 - Hypotensive effect associated with a phospholipase c-delta 1 gene mutation in the spont... 22588575 - Modeling the impact of partial hepatectomy on the hepatic hemodynamics using a rat model. 7416665 - Laryngeal regulation of airway resistance. i. chemoreceptor reflexes. 7619355 - Changes of vascular architecture independent of blood pressure in experimental uremia. |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2006-01-03 |
Journal Detail:
|
Title: Hypertension Volume: 47 ISSN: 1524-4563 ISO Abbreviation: Hypertension Publication Date: 2006 Mar |
Date Detail:
|
Created Date: 2006-02-17 Completed Date: 2006-03-17 Revised Date: 2007-08-13 |
Medline Journal Info:
|
Nlm Unique ID: 7906255 Medline TA: Hypertension Country: United States |
Other Details:
|
Languages: eng Pagination: 603-8 Citation Subset: IM |
Affiliation:
|
BHF Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom. sp24g@clinmed.gla.ac.uk |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adrenergic beta-Antagonists
/
therapeutic use Aged Angiotensin II Type 1 Receptor Blockers / therapeutic use Angiotensin-Converting Enzyme Inhibitors / therapeutic use Antihypertensive Agents / therapeutic use* Blood Pressure / drug effects* Calcium Channel Blockers / therapeutic use Chromosomes, Human, Pair 2* Diuretics / therapeutic use Female Genome, Human Humans Hypertension / drug therapy*, genetics, physiopathology* Linkage (Genetics)* Lod Score Male Middle Aged |
| Grant Support | |
ID/Acronym/Agency:
|
066780/Z/01/Z//Wellcome Trust |
| Chemical | |
Reg. No./Substance:
|
0/Adrenergic beta-Antagonists; 0/Angiotensin II Type 1 Receptor Blockers; 0/Angiotensin-Converting Enzyme Inhibitors; 0/Antihypertensive Agents; 0/Calcium Channel Blockers; 0/Diuretics |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Enhanced endothelin synthesis by endothelial cells exposed to sera from pregnant rats with decreased...
Next Document: Glucagon receptor-mediated extracellular signal-regulated kinase 1/2 phosphorylation in rat mesangia...