Interaction Between
            <i>ACE</i>
            and
            <i>ADD1</i>
            Gene Polymorphisms in the Progression of IgA Nephropathy in Japanese Patients

Narita, Ichiei; Goto, Shin; Saito, Noriko; Song, Jukun; Ajiro, Junya; Sato, Fuminori; Saga, Daisuke; Kondo, Daisuke; Akazawa, Kohei; Sakatsume, Minoru; Gejyo, Fumitake

doi:10.1161/01.hyp.0000085193.25617.78

Cited by 31 publications

(17 citation statements)

References 36 publications

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“…Consistently, Wang et al (96) observed that, in 1454 subjects randomly selected from a white population, those with the combined presence of the W and D alleles of the ADD1 G460W and ACE I/D polymorphisms, respectively, were at increased risk of renal disease. The WW genotype was also associated with faster progression in Japanese patients with IgA nephropathy when combined with the II ACE genotype (97). Thus, the above preliminary findings provide some evidence that polymorphisms of components of non-RAS pathways, in combination with different ACE I/D genotypes, may affect the risk of development and progression of chronic kidney disease.…”

Section: Other Non-ras Polymorphisms and Their Interactions With The mentioning

confidence: 64%

Angiotensin Converting Enzyme Insertion/Deletion Polymorphism and Renoprotection in Diabetic and Nondiabetic Nephropathies

Ruggenenti

Bettinaglio

Pinares

et al. 2008

Clinical Journal of the American Society of Nephrology

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Despite the huge amount of studies looking for candidate genes, the ACE gene remains the unique, well-characterized locus clearly associated with pathogenesis and progression of chronic kidney disease, and with response to treatment with drugs that directly interfere with the renin angiotensin system (RAS), such as angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists (ARA). The II genotype is protective against development and progression of type I and type II nephropathy and is associated with a slower progression of nondiabetic proteinuric kidney disease. ACE inhibitors are particularly effective at the stage of normoalbuminuria or microalbuminuria in both type I and type II diabetics with the II genotype, whereas the DD genotype is associated with a better response to ARA therapy in overt nephropathy of type II diabetes and to ACE inhibitors in male patients with nondiabetic proteinuric nephropathies. The role of other RAS or non-RAS polymorphisms and their possible interactions with different ACE I/D genotypes are less clearly defined. Thus, evaluating the ACE I/D polymorphism is a reliable tool to identify patients at risk and those who may benefit the most of renoprotective therapy with ACE inhibitors or ARA. This may guide pharmacologic therapy in individual patients and help design clinical trials in progressive nephropathies. Moreover, it might help optimize prevention and intervention strategies at population levels, in particular, in countries where resources are extremely limited and 1 million patients continue to die every year of cardiovascular or renal disease.

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Section: Other Non-ras Polymorphisms and Their Interactions With The mentioning

confidence: 64%

Angiotensin Converting Enzyme Insertion/Deletion Polymorphism and Renoprotection in Diabetic and Nondiabetic Nephropathies

Ruggenenti

Bettinaglio

Pinares

et al. 2008

Clinical Journal of the American Society of Nephrology

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“…Twelve (8,9,14,48,106,110,111,117,118,148,150,155) of 16 (103,107,115,162) studies found that ADD1 polymorphism alone or in combination with that of ACE positively associates with stroke or coronary heart disease or renal or vascular dysfunctions. In conclusion, when context is taken into account, the results obtained both in rats and in humans are consistent with the notion that the interaction among the adducin loci or between ADD1 and ACE are involved in human and rat hypertension and related disorders.…”

Section: Studies In Humansmentioning

confidence: 99%

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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“…[3] Several studies about the ACE I/D gene polymorphisms in VUR patients have revealed that the D allele might be a risk factor for renal parenchymal damage in children. [7][8][9] Also, the DD genotype has been reported to be associated with reduced renal function in patients with chronic renal diseases like Ig A nephropathy, [10][11][12] focal segmental glomerulosclerosis, [13,14] diabetic nephropathy, [15,16] polycystic kidney disease, [17] and tubulointerstitial nephritis. [18] Because tubulointerstitial damage is also common in VUR, the ACE polymorphism is of interest in this patient group, as it may give clues about the progression of the renal scarring.…”

Section: Introductionmentioning

confidence: 99%

Renin-Angiotensin System Polymorphisms: A Risk Factor for Progression to End-Stage Renal Disease in Vesicoureteral Reflux Patients

et al. 2009

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Aim. Renin-angiotensin system (RAS) gene mutations have been implicated as a risk factor for the presence and progression of renal disease in vesicoureteral reflux (VUR). However, the results are contradictory, and the effects of RAS polymorphisms in VUR patients with end-stage renal disease (ESRD) have not been defined yet. This study was designed to evaluate the angiotensin-converting enzyme insertion/deletion (ACE-I/D), angiotensinogen (AGT) M235T, and angiotensin II receptor type 1 (ATR1) A1166C and type 2 (ATR2) C3123A gene polymorphisms as risk factors for progression to ESRD in patients with VUR. Methods. ACE-I/D, AGT-M235T, ATR1-A1166C, and ATR2-C3123A were identified in 161 ESRD patients (52 female, 109 male; 77 renal transplant, 84 dialysis; age: 34.4 ± 11.2 years). VUR was the ESRD etiology in 40 patients. Genetic polymorphisms of the ACE gene I/D, AGT gene M235T, ATR1 gene A1166C, and ATR2 gene C3123A were identified in all of the patients. Results. We detected no linkage between genetic polymorphisms of ATR1-, ATR2-, AGT-, and VUR-related ESRD. When ACE gene was considered, VUR(+) patients had 63.6% DD, 36.4% ID, and no II alleles, whereas VUR(−) patients had 48.6% DD, 43.2% ID, and 8.1% II alleles. Conclusion. A striking feature of VUR-related ESRD patients was the absence of II alleles, so the DD genotype may be accepted as a genetic susceptibility factor for progression to ESRD in VUR patients.

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Interaction Between ACE and ADD1 Gene Polymorphisms in the Progression of IgA Nephropathy in Japanese Patients

Cited by 31 publications

References 36 publications

Angiotensin Converting Enzyme Insertion/Deletion Polymorphism and Renoprotection in Diabetic and Nondiabetic Nephropathies

Angiotensin Converting Enzyme Insertion/Deletion Polymorphism and Renoprotection in Diabetic and Nondiabetic Nephropathies

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

Renin-Angiotensin System Polymorphisms: A Risk Factor for Progression to End-Stage Renal Disease in Vesicoureteral Reflux Patients

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