Effects of three candidate genes on prevalence and incidence of hypertension in a Caucasian population

被引:198
作者
Staessen, JA
Wang, JG
Brand, E
Barlassina, C
Birkenhäger, WH
Herrmann, SM
Fagard, R
Tizzoni, L
Bianchi, G
机构
[1] Katholieke Univ Leuven, Dept Mol Cardiovasc Res, Study Coordinating Ctr, Lab Hypertens Hypertens Cardiovasc Rehabil Unit, B-3000 Louvain, Belgium
[2] Free Univ Berlin, Klinikum Benjamin Franklin, D-12200 Berlin, Germany
[3] Univ Milan, Osped San Raffaele, Dipartimento Sci & Tecnol Biomed, Div Nefrol Dialisi & Ipertensione, I-20127 Milan, Italy
[4] Erasmus Univ, Rotterdam, Netherlands
关键词
angiotensin converting enzyme; aldosterone synthase; alpha-adducin; blood pressure; candidate gene; hypertension;
D O I
10.1097/00004872-200108000-00002
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Background The genes encoding angiotensin converting enzyme (ACE, I/D), ct-adducin (ADD, Gly460Trp) and aldosterone synthase (AS, -344C/T) share the potential of influencing blood pressure (BP) via sodium homeostasis. However, most studies in humans focused on single-gene effects and disregarded epistasis, the suppression or potentiation of a gene by other non-allelic genes. Methods We studied the singular and combined effects of the aforementioned candidate genes: (1) in relation to BID, plasma renin activity (PRA) and urinary aldosterone in 1461 subjects randomly selected from a Caucasian population; and (2) in relation to the incidence of hypertension in a subgroup of 678 initially normotensive subjects followed up for 9.1 years (median). Results In cross-sectional analyses, AS/CC homozygosity was associated with slightly lower systolic BP (-1.32 mmHg; P = 0.08). AS/TT homozygotes showed both lower PRA and higher urinary aldosterone excretion (P less than or equal to 0.05). In multiple-gene analyses, compared with the whole study population, ADD/Trp subjects had a higher relative risk of hypertension in the presence of the AS/T allele (1.29; P = 0.05), whereas in combination with AS/CC homozygosity ADD/Trp subjects had the smallest relative risk (0.48; P = 0.003). Hypertension developed in 229 subjects (36.6 cases per 1000 person-years). ACE/DD homozygosity, in comparison with the other ACE genotypes, was associated with increases in the incidence of hypertension, which amounted to 31% (P = 0.005) in single-gene analyses, to 59% (P = 0.004) in carriers of the ADD/Trp allele and to 122% (P = 0.0007) in AS/CC subjects. Among subjects who had both the ADD/Trp allele and the AS/CC genotype, ACE/DD homozygotes manifested a 252% (P = 0.001) higher incidence of hypertension. Conclusions Epistatic interactions between the ACE, ADD and AS genes contribute to the prevalence and incidence of hypertension in Caucasians. The clinical relevance of the risk-conferring haplotypes identified in our prospective study was underscored by their positive predictive values, which under the assumption of a 20% life-time risk of hypertension, ranged from 29.8-40.1%. (C) 2001 Lippincott Williams & Wilkins.
引用
收藏
页码:1349 / 1358
页数:10
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