The 460Trp polymorphism of the human α-adducin gene is not associated with isolated systolic hypertension in elderly Australian Caucasians

Alam, Shahin; Liyou, Nancy E.; Davis, Darren R.; Tresillian, Michael; Ag, Johnson

doi:10.1038/sj.jhh.1000944

Cited by 17 publications

(11 citation statements)

References 16 publications

(24 reference statements)

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“…Further, we also analyzed the association between ADD1 Gly460Trp polymorphism and essential hypertension by combining 15 case-control studies, involving 3187 cases and 3720 controls[913–2224–27] as shown in Table 4. Surprisingly, the overall prevalence of 460Trp allele was higher in control subjects that amounted to 34.7% as compared to 32% in cases.…”

Section: Resultsmentioning

confidence: 99%

Gly460Trp polymorphism of the ADD1 gene and essential hypertension in an Indian population: A meta-analysis on hypertension risk

et al. 2010

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BACKGROUND:Essential hypertension is a complex genetic trait. Genetic variant of alpha adducin (ADD1) gene have been implicated as a risk factor for hypertension. Given its clinical significance, we investigated the association between ADD1 Gly460Trp gene polymorphism and essential hypertension in an Indian population. Further, a meta-analysis was carried out to estimate the risk of hypertension.METHODS:In the current study, 432 hypertensive cases and 461 healthy controls were genotyped for the Gly460Trp ADD1 gene polymorphism. Genotyping was determined by real time PCR using Taqman assay. Multiple logistic regression analysis was used to detect the association between Gly460Trp polymorphism and hypertension.RESULTS:No significant association was found in the genotype and allele distribution of Gly460Trp polymorphism with hypertension in our study. A total of 15 case-control studies were included in the meta-analysis. There was no evidence of the association of Gly460Trp polymorphism with hypertension in general or in any of the sub group.CONCLUSIONS:We found that the Gly460Trp polymorphism is not a risk factor for essential hypertension in a south Indian Tamilian population. However, the role of ADD1 polymorphism may not be excluded by a negative association study. Further, large and rigorous case-control studies that investigate gene–gene–environment interactions may generate more conclusive claims about the molecular genetics of hypertension.

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Section: Resultsmentioning

confidence: 99%

Gly460Trp polymorphism of the ADD1 gene and essential hypertension in an Indian population: A meta-analysis on hypertension risk

et al. 2010

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“…Population-based and hospital-based studies were all included in our meta-analysis. Twelve studies were population-based [9], [13], [20], [22], [23], [25]–[28], [30]–[32], and ten were hospital-based studies [6]–[8], [10]–[12], [21], [24], [29], [33]. Populations among these studies were as following: ten studies were Caucasians or European descent (7632 cases and 8588 controls), nine studies were East Asians (5957 cases and 6770 controls) and three studies were others (one study recruited South African Negro subjects and the other two studies recruited African-American subjects) involving 714 cases and 603 controls.…”

Section: Resultsmentioning

confidence: 99%

Alpha-Adducin Gly460Trp Polymorphism and Hypertension Risk: A Meta-Analysis of 22 Studies Including 14303 Cases and 15961 Controls

Liu

Huang

et al. 2010

PLoS ONE

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BackgroundNo clear consensus has been reached on the alpha-adducin polymorphism (Gly460Trp) and essential hypertension risk. We performed a meta-analysis in an effort to systematically summarize the possible association.Methodology/Principal FindingsStudies were identified by searching MEDLINE and EMBASE databases complemented with perusal of bibliographies of retrieved articles and correspondence with original authors. The fixed-effects model and the random-effects model were applied for dichotomous outcomes to combine the results of the individual studies. We selected 22 studies that met the inclusion criteria including a total of 14303 hypertensive patients and 15961 normotensive controls. Overall, the 460Trp allele showed no statistically significant association with hypertension risk compared to Gly460 allele (P = 0.69, OR = 1.02, 95% CI 0.94–1.10, Pheterogeneity<0.0001) in all subjects. Meta-analysis under other genetic contrasts still did not reveal any significant association in all subjects, Caucasians, East Asians and others. The results were similar but heterogeneity did not persist when sensitivity analyses were limited to these studies.Conclusions/SignificanceOur meta-analysis failed to provide evidence for the genetic association of α-adducin gene Gly460Trp polymorphism with hypertension. Further studies investigating the effect of genetic networks, environmental factors, individual biological characteristics and their mutual interactions are needed to elucidate the possible mechanism for hypertension in humans.

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“…In 10 populations, a positive association was found (10,13,32,42,80,116,119,124,156), whereas in two populations, a positive association was found only in women (128) or young subjects (132). In 13 populations, no association was present (2,3,38,70,74,79,84,88,100,116,119,124,151). In three studies (116,119,124), both positive and negative associations are observed in different populations.…”

Section: Studies In Humansmentioning

confidence: 86%

Genetic variations of tubular sodium reabsorption leading to “primary” hypertension: from gene polymorphism to clinical symptoms

Bianchi

2005

American Journal of Physiology-Regulatory, Integrative and Comp

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Bianchi, Giuseppe. Genetic variations of tubular sodium reabsorption leading to "primary" hypertension: from gene polymorphism to clinical symptoms. Am J Physiol Regul Integr Comp Physiol 289: R1536-R1549, 2005. doi:10.1152/ajpregu.00441.2005.-The definition of the most appropriate strategy to demonstrate causation of a given geneticmolecular mechanism in a complex multifactorial polygenic disease like hypertension is hampered by the underestimation of the complexity arising from the genetic and environmental interactions. To disentangle this complexity, we developed a strategy based on six steps: 1) isolation of a rodent model of hypertension (Milan hypertensive strain and Milan normotensive strain) that shares some pathophysiological abnormalities with human primary hypertension; 2) definition in the model of the sequence of events linking these abnormalities to a genetic molecular mechanism; 3) determination of the polymorphism of the three adducin genes discovered in the model both in rats and in humans; 4) comparison at biochemical and physiological levels between the rodent models and the hypertensive carriers of the "mutated" gene variants; 5) evaluation of the impact of the adducin genes in hypertension and its organ complications with association and linkage studies in humans, also considering the genetic and environmental interactions; and 6) development of a pharmacogenomic approach aimed at establishing the therapeutic benefit of a drug interfering with the sequence of events triggered by adducin and their effect's size. The bulk of data obtained demonstrates the importance of a multidisciplinary approach considering a variety of genetic and environmental interactions. Adducin functions within the cells as a heterodimer composed of a combination of three subunits. Each of these subunits is coded by genes mapping to different chromosomes. Therefore, the interaction among these genes, taken together with the interactions with other modulatory genes or with the environment, is indispensable to establish the adducin clinical impact. The hypothesis that adducin polymorphism favors the development of hypertension via an increased tubular sodium reabsorption is well supported by a series of consistent experimental and clinical data. Many mechanistic aspects, underlying the link between these genes and clinical symptoms, need to be clarified. The clinical effect size of adducin must be established also with the contribution of pharmacogenomics with a drug that selectively interferes with the sequence of events triggered by the mutated adducin.genes; blood pressure; Na-K pump; Na channel; adducin The difficulty lies, not only in the new ideas, but in escaping the old ones. J. M. Keynes STARLING'S LONG-LASTING concern was to use physiology as a means to bring basic science to the bedside. Indeed, by integrating the capillary fluid exchange with the cardiac pump function, Starling provided a substantial contribution to bridge the gap between the contemporary basic science of circulation and the clinical sympto...

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The 460Trp polymorphism of the human α-adducin gene is not associated with isolated systolic hypertension in elderly Australian Caucasians

Cited by 17 publications

References 16 publications

Gly460Trp polymorphism of the ADD1 gene and essential hypertension in an Indian population: A meta-analysis on hypertension risk

Gly460Trp polymorphism of the ADD1 gene and essential hypertension in an Indian population: A meta-analysis on hypertension risk

Alpha-Adducin Gly460Trp Polymorphism and Hypertension Risk: A Meta-Analysis of 22 Studies Including 14303 Cases and 15961 Controls

Genetic variations of tubular sodium reabsorption leading to “primary” hypertension: from gene polymorphism to clinical symptoms

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