IDENTIFICATION OF ESSENTIAL-HYPERTENSION GENES

Objectives: To review approaches used to identify genetic loci having aetiological involvement in essential hypertension and to highlight the advantages and limitations of each. Contents: Cross-sectional analyses are reasonably powerful, require no knowledge of mode of transmission and have been used to show the association of variants of the insulin receptor, dipeptidyl carboxypeptidase-1 and glucocorticoid receptor genes with hypertension, using relatively low numbers of subjects having a strong genetic component to their elevated blood pressure. Association methods test only a minute portion of the genome, however, and rely heavily on 'linkage disequilibrium' between the marker and causative locus. Approaches involving linkage analysis are not so constrained. Obtaining suitable large affected families in a complex, polygenic, quantitative disease such as hypertension is, however, difficult, and this is compounded by the late onset of the disease, its unknown penetrance, variable phenotype and the influence of environmental factors. The use of only affected pedigree members is more straightforward, requires fewer assumptions and has been used to implicate the angiotensinogen gene in hypertension. Conclusion: Cross-sectional and sib-pair approaches show promise in identification of human hypertension genes.