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

Staessen, Jan A.; Wang, Tzung‐Dau; Brand, Erwin; Barlassina, Cristina; Birkenhäger, W. H.; Herrmann, Stefan-Martin; Fagard, Robert; Tizzoni, Laura; Bianchi, Giuseppe

doi:10.1097/00004872-200108000-00002

Cited by 219 publications

(220 citation statements)

References 40 publications

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“…In the same population the ACE I/D, a-adducin Gly460Trp and aldosterone synthase 344C/T polymorphisms showed significant interactions in relation to the intima-media thickness of the femoral artery [2] and the incidence of hypertension [3]. The hypothesis underlying our previous studies [1,2,3,4] was that these three candidate genes and their interactions lead to structural and/or functional changes in the cardiovascular-renal system via their influence on sodium reabsorption in the kidney and the circulating fluid volume.…”

Section: Introductionmentioning

confidence: 81%

Renal function in relation to three candidate genes in a Chinese population

et al. 2004

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We recently found in a white population that the genes encoding angiotensin-converting enzyme (ACE, I/D polymorphism), a-adducin (Gly460Trp), and aldosterone synthase ( 344C/T) jointly influence renal function. We therefore investigated in a Chinese population the associations between the serum concentrations of creatinine and uric acid and these three genetic polymorphisms. We genotyped 471 ethnic Han Chinese subjects from 125 nuclear families recruited in northern China via random population sampling (75%) and at specialized hypertension clinics (25%). We performed population-based and family-based association analyses using generalized estimating equations (GEE) and quantitative transmission disequilibrium test (QTDT), respectively, while controlling for covariables. The participants were 39.7 years old and included 235 women (49.9%). The blood pressure measured at the subjects' homes averaged 126/80 mmHg. Mean values were 71 mol/l for serum creatinine, 111 ml min 1 1.73 m 2 for calculated creatinine clearance, and 236 mol/l for serum uric acid. With adjustment for covariables, GEE analyses of single genes demonstrated that serum uric acid, but not serum creatinine, was positively associated with the ACE D allele. Serum uric acid concentrations were 15.8 mol/l (95% confidence interval 3.3-28.2) and 25.7 mol/l (11.1-40.2) higher in DD homozygotes than in ID and II subjects, respectively. Further GEE analyses of the three genes combined showed that the association between serum uric acid and the ACE polymorphism was confined to carriers of the a-adducin Gly and/or aldosterone synthase C alleles. Sensitivity analyses in parents and offspring separately as well as QTDT analyses were confirmatory. Among 114 informative offspring carrying the a-adducin Gly allele serum uric acid was significantly and positively associated with the transmission of the ACE D allele (b=20.7 mol/l). In conclusion, the present study extends our previous findings on the combined effects of the three candidate genes and supports the concept that these genetic polymorphisms jointly influence renal function.

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Section: Introductionmentioning

confidence: 81%

Renal function in relation to three candidate genes in a Chinese population

et al. 2004

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“…38,43 This is because complex trait diseases such as EH are not regulated by single-gene effects but are often associated with multiple genetic and environmental factors. In the present study, we examined a significant interaction between the GNB3 and ACE genes.…”

Section: Discussionmentioning

confidence: 99%

“…1 The evaluation of gene-gene interactions rather than the determination of single-gene effects is crucial to understanding any genetic influences. 38,43 K The associations between GNB3 C825T and ACE I/D polymorphisms and hypertension have been carried out, but found conflicting results in ethnic backgrounds. 23,44 What this study adds K The interaction between the GNB3 825T and ACE D alleles was found to be significantly associated with hypertension in this study.…”

Section: Discussionmentioning

confidence: 99%

Interaction between GNB3 C825T and ACE I/D polymorphisms in essential hypertension in Koreans

et al. 2006

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Essential hypertension (EH) is considered a typical polygenic disease, so the evaluation of gene-gene interactions rather than the determination of single gene effects is crucial to understanding any genetic influences. The G-protein b3-subunit (GNB3) 825T allele, associated with enhanced G-protein signalling, is a strong candidate for interactions with polymorphisms, such as insertion/deletion (I/D) polymorphism of angiotensin I-converting enzyme (ACE) gene. We investigated whether there is an association between GNB3 C825T and ACE I/D polymorphisms for the development of EH. We carried out a case-control study of 688 hypertensive and 924 normotensive subjects recruited from South Korea. The GNB3 C825T and ACE I/D genotypes were determined by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism methods, respectively. The distributions of alleles and genotypes for the GNB3 C825T and ACE I/D polymorphisms were not found to be significantly associated with hypertensive status in either males or females. Logistic regression analysis indicated that the GNB3 825T allele carriers were positively associated with EH in males (odds ratio (OR) for TT/CT, 1.459; 95% confidence interval (CI), 1.048-2.033, P ¼ 0.0255). In analysis of gene-gene interaction, we found that there was a significant interaction between the GNB3 825T and ACE D alleles (Po0.05). OR for EH was significantly higher in 825T allele carriers with ACE D allele (OR, 1.490; 95% CI, 1.117-1.987, P ¼ 0.0067). A significant interaction between the GNB3 825T and the ACE D alleles may contribute to the predisposing effect for the development of EH in Koreans.

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“…Other groups refuted these results (Schmidt et al 1997;Zhang et al 2000;Staessen et al 2001;Iliadou et al 2002;Ono et al 2003). Overall, it remains open whether there is a relevant association between the AT1R A1166C polymorphism and hypertension.…”

Section: Genetic Variants In the Angiotensin II Receptor Type Imentioning

confidence: 97%

Genetics of arterial hypertension and hypotension

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Schürks

Rimmbach

et al. 2007

Naunyn-Schmied Arch Pharmacol

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Human hypertension affects affects more than 20% of the adult population in industrialized countries, and it is implicated in millions of deaths worldwide each year from stroke, heart failure and ischemic heart disease. Available evidence suggests a major genetic impact on blood pressure regulation. Studies in monogenic hypertension revealed that renal salt and volume regulation systems are predominantly involved in the genesis of these disorders. Mutations here affect the synthesis of mineralocorticoids, the function of the mineralocorticoid receptor, epithelial sodium channels and their regulation by a new class of kinases, termed WNK kinases. It has been learned from monogenic hypotension that almost all ion transporters involved in the renal uptake of Na + have a major impact on blood pressure regulation. For essential hypertension as a complex disease, many candidate genes have been analysed. These include components of the reninangiotensin-aldosterone system, adducin, β-adrenoceptors, G protein subunits, regulators of G protein signalling (RGS) proteins, Rho kinases and G protein receptor kinases. At present, the individual impact of common polymorphisms in these genes on the observed blood pressure variation, on risk for stroke and as predictors of antihypertensive responses remains small and clinically irrelevant. Nevertheless, these studies have greatly augmented our knowledge on the regulation of renal functions, cellular signal transduction and the integration of both. Together, this provides the basis for the identification of novel drug targets and, hopefully, innovative antihypertensive drugs.

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

Cited by 219 publications

References 40 publications

Renal function in relation to three candidate genes in a Chinese population

Renal function in relation to three candidate genes in a Chinese population

Interaction between GNB3 C825T and ACE I/D polymorphisms in essential hypertension in Koreans

Genetics of arterial hypertension and hypotension

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