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

Wang, Tzung‐Dau; Liu, Lifang; Zagato, Laura; Xie, Jingyi; Fagard, Robert; Jin, K. G.; Wang, Jinxiang; Li, Yan; Bianchi, Giuseppe; Staessen, Jan A.; Liu, Lisheng

doi:10.1007/s00109-004-0574-8

Cited by 5 publications

(5 citation statements)

References 47 publications

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“…For the distribution of the ACE I/D polymorphism, the D allele frequency of the Koreans in the present study (39.6%) was much lower than that of African Americans (63%) 11 and Caucasians (64%), 39 but was higher than that of Australian Aborigines (12.6%) 40 and Amerindians (26.5%), 41 and similar to those described for Chinese Han (38%) 42 and mainland Japanese populations (40%). 17 Several reports have shown that ACE I/D polymorphism accounts for half of the variance of plasma ACE levels in the RAAS pathway.…”

Section: Discussionsupporting

confidence: 82%

“…14 Therefore, because AT-II receptors are typical G-protein-coupled receptors, it is very likely that D allele associated with elevated ACE concentrations may prove to be pathophysiological in individuals whose genetic structure is composed of an allelic variant that causes increased cellular responsiveness. 42 Thus, the GNB3 825T allele is an important marker to study for interactions with the ACE D allele.…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 82%

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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“…Use of a prospective design in a cohort protects against confounding by population stratification. Furthermore, our prospective epidemiological results corroborate a hypothesis independently raised by studies in never-treated hypertensive patients, 11,12 previous population surveys, [13][14][15][16] and pharmacogenomic studies, 32,33 and they are supported by animal experiments 26 and an established pathogenetic mechanism. 9,10 Moreover, we replicated our initial findings in human fibroblasts in kidney cells of human origin transfected by the wild-type and mutated human ADD1.…”

Section: Discussionsupporting

confidence: 86%

“…9 Substitution of glycine by tryptophan in the cytoskeleton protein ␣-adducin (ADD1 Gly460Trp) enhances tubular sodium reabsorption in the kidney. 9,10 Studies of never-treated hypertensive patients 11,12 and European [13][14][15] and Chinese populations 16 suggested that cardiovascular risk factors are associated with the ACE D allele, but only in the presence of mutated ADD1. Here, we report the results of a prospective population study and cell experiments, which further clarify the interaction between these 2 polymorphisms from a prognostic and mechanistic point of view.…”

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confidence: 99%

Angiotensin-Converting Enzyme I/D and α-Adducin Gly460Trp Polymorphisms

Zagato

Kuznetsova

et al. 2007

Hypertension

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Abstract-The angiotensin-converting enzyme (ACE) I/D and the ␣-adducin (ADD1) Gly460Trp polymorphisms are associated with cardiovascular risk factors. In a prospective population study and in cell models, we investigated the combined effects of these 2 polymorphisms. We randomly recruited 1287 white subjects (women: 50.0%; mean age: 55.9 years). We obtained outcomes from registries and repeat examinations (median 3). Over 9.0 years (median), 178 fatal or nonfatal cardiovascular events occurred. In ADD1 Trp allele carriers, the multivariate-adjusted hazard ratios associated with ACE DD versus I were 1.72 (Pϭ0.007) for total mortality, 2.35 (Pϭ0.02) for cardiovascular mortality, 2.02 (Pϭ0.005) for all cardiovascular events, and 2.59 (Pϭ0.03) for heart failure. In contrast, these hazard ratios did not reach significance in ADD1 GlyGly homozygotes (0.08ՅPՅ0.90). The positive predictive value and attributable risk associated with ACE DD homozygosity combined with mutated ADD1 were 36.2% and 10.3%, respectively. To clarify our epidemiological observations, we investigated the effects of mutated human ADD1 on the membrane-bound ACE activity in fibroblasts from 51 volunteers and in transfected human embryonic kidney cells (31 experiments). In fibroblasts (5.10 versus 3.63 nanomoles of generated hippuric acid per milligram of protein per minute; Pϭ0.0021) and human embryonic kidney cells (1.086 versus 0.081 nmol/mg per minute; Pϭ0.017), the membrane-bound ACE activity increased in the presence but not absence of the ADD1 Trp allele. In conclusion, the combination of ACE DD homozygosity and mutated ADD1 worsened cardiovascular prognosis to a similar extent as classic risk factors, possibly because of increased membrane-bound ACE activity in subjects carrying the ADD1 Trp allele. Key Words: adducin Ⅲ angiotensin-converting enzyme Ⅲ clinical genetics Ⅲ epidemiology Ⅲ risk factors I n monogenic diseases with typical Mendelian inheritance, such as phenylketonuria 1 or thalassanemia, 2 penetrance is under the influence of endogenous modulators, lifestyle, and environmental factors. The same mutation can, therefore, produce a wide spectrum of clinical manifestations, ranging from early onset debilitating disease to just mild symptoms at advanced age. This principle is even more applicable to polygenic cardiovascular disorders, in which many genes to a small and variable extent contribute to a common disease.The insertion-deletion polymorphism of the angiotensinconverting enzyme (ACE) gene (ACE I/D) is among the most frequently examined genetic variants in cardiovascular medicine. 3 It affects the plasma level of ACE 3 and the generation of angiotensin II in the kidney, 4 -6 arterial wall, 7 and heart. 8 The sodium content of the body modulates the effects of angiotensin II. 9 Substitution of glycine by tryptophan in the cytoskeleton protein ␣-adducin (ADD1 Gly460Trp) enhances tubular sodium reabsorption in the kidney. 9,10 Studies of never-treated hypertensive patients 11,12 and European 13-15 and Chinese populations 16 suggest...

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“…However, we adjusted for alcohol intake in our models to assess the relation between increased uric acid concentrations and incident hypertension. Recently, it has been shown that uric acid is positively associated with the gene encoding angiotensin-converting enzyme (ACE, I/D polymorphism) in a Chinese population (36,37 ). Thus, we could not exclude the possibility that genetic variants may contribute to the association between uric acid and the risk of developing hypertension.…”

Section: Discussionmentioning

confidence: 96%