Genetics of hypertension: from experimental models to clinical applications

被引:29
作者
Lee, WK [1 ]
Padmanabhan, S [1 ]
Dominiczak, AF [1 ]
机构
[1] Univ Glasgow, Western Infirm, Dept Med & Therapeut, BHF,Blood Pressure Grp, Glasgow G11 6NT, Lanark, Scotland
基金
英国医学研究理事会;
关键词
quantitative trait loci; essential hypertension; congenic strains; linkage analysis; candidate genes; monogenic hypertension;
D O I
10.1038/sj.jhh.1001043
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Human essential hypertension is a complex, multifactorial, quantitative trait under a polygenic control. Over the last decade several strategies have been used to dissect the genetic determinants of hypertension. Of these strategies, the study of rare monogenic forms of hypertension has been the most successful. Attempts to identify the multiple genes involved in the more common polygenic form of hypertension has been more difficult. Many laboratories use rat models of genetic hypertension where some of the complexity of studying human hypertension can be removed. Numerous crosses between hypertensive and normotensive strains have produced several quantitative trait loci (QTL) for blood pressure and other related phenotypes such as left ventricular hypertrophy, stroke, insulin resistance and kidney failure. In this review we describe established and novel strategies to dissect the susceptibility and severity loci for human essential hypertension. We also illustrate a few successful examples of a direct translation of genetic discoveries from the experimental setting to human investigation. The use of new molecular tools such as gene 'chips' or microarrays for either gene expression profiling or single nucleotide polymorphisms (SNPs)-based total genome scanning strategies will ultimately result in new diagnostics and therapeutics for human essential hypertension.
引用
收藏
页码:631 / 647
页数:17
相关论文
共 197 条
[81]   Independent genetic susceptibility to cardiac hypertrophy in inherited hypertension [J].
Innes, BA ;
McLaughlin, MG ;
Kapuscinski, MK ;
Jacob, HJ ;
Harrap, SB .
HYPERTENSION, 1998, 31 (03) :741-746
[82]   No association between α-adducin 460 polymorphism and essential hypertension in a Japanese population [J].
Ishikawa, K ;
Katsuya, T ;
Sato, N ;
Nakata, Y ;
Takami, S ;
Takiuchi, S ;
Fu, YX ;
Higaki, J ;
Ogihara, T .
AMERICAN JOURNAL OF HYPERTENSION, 1998, 11 (04) :502-506
[83]   Isolation of a chromosome 1 region that contributes to high blood pressure and salt sensitivity [J].
Iwai, N ;
Tsujita, Y ;
Kinoshita, M .
HYPERTENSION, 1998, 32 (04) :636-638
[84]   GENETIC-MAPPING OF A GENE CAUSING HYPERTENSION IN THE STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RAT [J].
JACOB, HJ ;
LINDPAINTNER, K ;
LINCOLN, SE ;
KUSUMI, K ;
BUNKER, RK ;
MAO, YP ;
GANTEN, D ;
DZAU, VJ ;
LANDER, ES .
CELL, 1991, 67 (01) :213-224
[85]   A GENETIC-LINKAGE MAP OF THE LABORATORY RAT, RATTUS-NORVEGICUS [J].
JACOB, HJ ;
BROWN, DM ;
BUNKER, RK ;
DALY, MJ ;
DZAU, VJ ;
GOODMAN, A ;
KOIKE, G ;
KREN, V ;
KURTZ, T ;
LERNMARK, A ;
LEVAN, G ;
MAO, YP ;
PETTERSSON, A ;
PRAVENEC, M ;
SIMON, JS ;
SZPIRER, C ;
SZPIRER, J ;
TROLLIET, MR ;
WINER, ES ;
LANDER, ES .
NATURE GENETICS, 1995, 9 (01) :63-69
[86]   825T allele of the G-protein β3 subunit gene (GNB3) is associated with impaired left ventricular diastolic filling in essential hypertension [J].
Jacobi, J ;
Hilgers, KF ;
Schlaich, MP ;
Siffert, W ;
Schmieder, RE .
JOURNAL OF HYPERTENSION, 1999, 17 (10) :1457-1462
[87]   GLUCOCORTICOID-SUPPRESSIBLE HYPERALDOSTERONISM - EFFECTS OF CROSSOVER SITE AND PARENTAL ORIGIN OF CHIMERIC GENE ON PHENOTYPIC-EXPRESSION [J].
JAMIESON, A ;
SLUTSKER, L ;
INGLIS, GC ;
FRASER, R ;
WHITE, PC ;
CONNELL, JMC .
CLINICAL SCIENCE, 1995, 88 (05) :563-570
[88]   Applicability of a "speed" congenic strategy to dissect blood pressure quantitative trait loci on rat chromosome 2 [J].
Jeffs, B ;
Negrin, CD ;
Graham, D ;
Clark, JS ;
Anderson, NH ;
Gauguier, D ;
Dominiczak, AF .
HYPERTENSION, 2000, 35 (01) :179-187
[89]   Sensitivity to cerebral ischaemic insult in a rat model of stroke is determined by a single genetic locus [J].
Jeffs, B ;
Clark, JS ;
Anderson, NH ;
Gratton, J ;
Brosnan, MJ ;
Gauguier, D ;
Reid, JL ;
Macrae, IM ;
Dominiczak, AF .
NATURE GENETICS, 1997, 16 (04) :364-367
[90]   Haplotypes of angiotensinogen in essential hypertension [J].
Jeunemaitre, X ;
Inoue, I ;
Williams, C ;
Charru, A ;
Tichet, J ;
Powers, M ;
Sharma, AM ;
GimenezRoqueplo, AP ;
Hata, A ;
Corvol, P ;
Lalouel, JM .
AMERICAN JOURNAL OF HUMAN GENETICS, 1997, 60 (06) :1448-1460