Functional genomics in hypertension.
OBJECTIVE
Essential hypertension is a complex polygenetic disease with a major impact on health worldwide. Despite earlier detection of promising candidate genes, only recent advances in genotyping technology and new approaches to examining gene and protein function have provided the tools to unravel the genetic basis of hypertension.


RESULTS
In humans, genome-wide scans resulted in the identification of several chromosomal loci that are linked to hypertension. These regions still contain a large number of potential candidate genes, but high-throughput genotyping methods will facilitate the detection and analysis of single-nucleotide polymorphisms within these genes. The focus will be on animal models of hypertension, specifically rats. Congenic strains facilitate the identification of genetic determinants of hypertension, and new technologies such as RNA interference (which silences the expression of target genes) and transgenic rescue models will help us to analyse the relationship between genes and function. Analysis of conserved synteny (preserved order of genes) between species allows translation of findings from rodent models to essential hypertension in humans. Recent discoveries and approaches beyond genomics will also be discussed, including the regulatory role of microRNA and the concept of proteomics.


CONCLUSIONS
The genetic basis of hypertension is complex, and the examination of the functional consequences of genetic variants in particular is still challenging. A number of tools are now available with which to examine gene-function relationships, and these will provide an improved understanding of cardiovascular genomics. This will eventually lead to targeted prevention and treatment strategies in patients with hypertension and other cardiovascular diseases.
McBride
Martin W
MW
BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
Graham
Delyth
D
Delles
Christian
C
Dominiczak
Anna F
AF
D000818:Animals; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D023281:Genomics; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology; D040901:Proteomics; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D012680:Sensitivity and Specificity
D012333:RNA, Messenger