Molecular genetics of human hypertension

被引:92
作者
Luft, FC
机构
[1] Franz Volhard Clin, D-13122 Berlin, Germany
[2] Humboldt Univ, Med Fak Charite, Max Delbruck Ctr Mol Med, D-1086 Berlin, Germany
关键词
hypertension; genetics; genes; salt-sensitivity; cardiovascular risk;
D O I
10.1097/00004872-199816121-00004
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
For the past decade, hypertension research has shifted strongly in the direction of molecular genetics. The success stories are the monogenic hypertensive syndromes. Classic linkage analyses has located the responsible genes for glucocorticoid-remediable aldosteronism, Liddle syndrome, and apparent mineralocorticoid excess. The genes have been cloned and their function elucidated. Other monogenic syndromes are currently being intensively studied. However, in the area of primary hypertension, the successes have relied on the candidate gene approach. Allelic variants in the genes for angiotensinogen, alpha-adducin, beta(2)-adrenergic receptor, the G-protein beta(3)-subunit and the T594M mutation in the beta-subunit of the epithelial sodium channel have been identified; however, the importance of these allelic variants to primary hypertension as a whole, is not yet clear. A variant in the angiotensin-converting enzyme gene could not, initially, be convincingly associated with hypertension, but more recent analyses suggest an influence of the deletion allele on blood pressure in men, but apparently not in women. In all likelihood we are dealing with many genes with small effects. Affected sibling pair linkage analyses will probably not be successful in identifying the loci of these genes. To find new genes, novel approaches will be necessary, including searching for quantitative trait loci linked to blood pressure in normotensive persons, haplotype sharing methodology in trios and family units, the use of better study designs, and the investigation of isolated populations. Finally, rethinking the phenotype 'hypertension' and its intermediates must also receive priority. J Hypertens 1998, 16:1871-1878 (C) 1998 Lippincott Williams & Wilkins.
引用
收藏
页码:1871 / 1878
页数:8
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