Combinational effect of genes for the renin–angiotensin system in conferring susceptibility to diabetic nephropathy

Osawa, Norihisa; Koya, Daisuke; Araki, Shin‐ichi; Uzu, Takashi; Tsunoda, Tatsuhiko; Kashiwagi, Atsunori; Nakamura, Yusuke; Maeda, Shiro

doi:10.1007/s10038-006-0090-5

Cited by 35 publications

(25 citation statements)

References 25 publications

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“…Along the same line, Bantis et al, described a synergistic association of AGT M235T and ACE I/D polymorphisms also with the progression of IgA nephropathy to ESKD (85) and found that those patients who carried more than two ACE-D or AGT-T alleles (that is the DD/TT, DD/MT, or ID/TT genotypes) were the ones with the largest benefit from ACE inhibitor therapy. In contrast with the above findings, however, Osawa et al (86) failed to detect any significant association of AT1R A1166C, ACE I/D, and AGT M235T polymorphisms with diabetic renal disease. Thus, whether and to what extent the interactions between AGT, and AT1R, and ACE polymorphisms may affect the progression of diabetic and nondiabetic chronic renal disease and response to RAS inhibitor therapy is still unclear.…”

Section: Other Ras Polymorphisms and Their Interactions With The Ace contrasting

confidence: 57%

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 Ras Polymorphisms and Their Interactions With The Ace contrasting

confidence: 57%

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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“…Bantis et al (49) reported an association between concomitant presence of ACE I/D and AGT M235T variants on the progression of IgG nephropathy to ESRD and better response to ACE inhibitor therapy in the presence of these variants. However, Subsequent report of Osawa et al (50) failed to indicate any significant interaction between ACE I/D, AGT M235T and AT1R A1166C variants on the risk of DN.…”

Section: Interaction Between Ace I/d and Variants Of Ras Genesmentioning

confidence: 93%

“…The role of two genes variants of angiotensinogen (AGT) and angiotensin II type-1 receptor (AT1R) and their interaction with ACE I/D polymorphism on the susceptibility to DN has been investigated with controversy (47)(48)(49)(50).…”

Section: Interaction Between Ace I/d and Variants Of Ras Genesmentioning

confidence: 99%

ACE insertion/deletion (I/D) polymorphism and diabetic nephropathy

Rahimi¹

2012

J Nephropathol

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Implication for health policy/practice/research/medical education:The presence of angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism affects the plasma level of ACE. ACE DD genotype is associated with highest systemic and renal ACE levels, compared with the lowest ACE activity in carriers of II genotype. Most studies confirmed that ACE I/D polymorphism is involved in the susceptibility to overt nephropathy with protective role of ACE II genotype against the disease in both type 1 and 2 diabetes mellitus. In this review focus has been performed on the study of ACE I/D polymorphism in various populations and its influence on the risk of onset and progression of diabetic nephropathy. Results:The presence of ACE insertion/deletion (I/D) polymorphism affects the plasma level of ACE. ACE DD genotype is associated with the highest systemic and renal ACE levels compared with the lowest ACE activity in carriers of II genotype. Conclusions: In this review focus has been performed on the study of ACE I/D polymorphism in various populations and its influence on the risk of onset and progression of diabetic nephropathy. Also, association between ACE I/D polymorphism and response to ACE inhibitor and angiotensin II receptor antagonists will be reviewed. Further, synergistic effect of this polymorphism and variants of some genes on the risk of development of diabetic nephropathy will be discussed.Review Article

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“…tensinogen, and the AT 1 receptor may be associated with complex multigenic diseases (41). The genetic variations inside the RAS that may affect the function of its components might have an influence on genetic predisposition to diabetes and renal and cardiovascular diseases (8,9,40,46). A better understanding of the relationship between the ability to increase vessel density in response to physiological electrical stimuli in adult skeletal muscle and the regulation of renin, a key enzyme in the production of ANG II, may bring new insights to the treatment of several diseases, since microvascular rarefaction and arteriolar remodeling are both necessary physiological adaptations that can become maladaptive and lead to target organ damage.…”

Section: Renin Gene Expression and Skeletal Muscle Angiogenesismentioning

confidence: 99%

Congenic strains reveal the effect of the renin gene on skeletal muscle angiogenesis induced by electrical stimulation

Resende

Amaral

Moreno

et al. 2008

Physiological Genomics

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de Resende MM, Amaral SL, Moreno C, Greene AS. Congenic strains reveal the effect of the renin gene on skeletal muscle angiogenesis induced by electrical stimulation. Physiol Genomics 33: 33-40, 2008. First published January 15, 2008 doi:10.1152/physiolgenomics.00150.2007.-Previous studies have indicated the importance of angiotensin II (ANG II) in skeletal muscle angiogenesis. The present study explored the effect of regulation of the renin gene on angiogenesis induced by electrical stimulation with the use of physiological, pharmacological, and genetic manipulations of the renin-angiotensin system (RAS). Transfer of the entire chromosome 13, containing the physiologically regulated renin gene, from the normotensive inbred Brown Norway (BN) rat into the background of an inbred substrain of the Dahl salt-sensitive (SS/Mcwi) rat restored renin levels and the angiogenic response after electrical stimulation. This restored response was significantly attenuated when SS-13 BN /Mcwi consomic rats were treated with lisinopril or high-salt diet. The role of ANG II on this effect was confirmed by the complete restoration of skeletal muscle angiogenesis in SS/Mcwi rats infused with subpressor doses of ANG II. Congenic strains derived from the SS-13 BN /Mcwi consomic were used to further verify the role of the renin gene in this response. Microvessel density was markedly increased after stimulation in congenic strains that contained the renin gene from the BN rat (congenic lines A and D). This angiogenic response was suppressed in control strains that carried regions of the BN genome just above (congenic line C) or just below (congenic line B) the renin gene. The present study emphasizes the importance of maintaining normal renin regulation as well as ANG II levels during the angiogenesis process with a combination of physiological, genetic, and pharmacological manipulation of the RAS. renin-angiotensin system; chromosomal substitution THE IMPORTANCE of the renin-angiotensin system (RAS) in controlling sodium homeostasis and vascular resistance is well established; however, in the past decade, much attention has been focused on the importance of angiotensin II (ANG II) as a regulator of microvessel density. Studies from our laboratory (2-4, 15, 37, 42) over the last 5 years have shown that ANG II is an essential component of the control system regulating microvessel density in the skeletal muscle. We have shown that inhibition of RAS activity with the use of pharmacological blockers of ANG II formation and blockade of the angiotensin type 1 (AT 1 ) receptor significantly attenuated the skeletal muscle angiogenic response of normotensive rats induced by exercise (3) and electrical stimulation (2). In addition, we found (37) that chronic infusion of ANG II, at subpressor doses, completely restored the angiogenesis response induced by electrical stimulation in rats fed a high-salt diet. The effects of high salt on microvascular structure and function in the absence of hypertension have been largely attributed to the suppress...

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Combinational effect of genes for the renin–angiotensin system in conferring susceptibility to diabetic nephropathy

Cited by 35 publications

References 25 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

ACE insertion/deletion (I/D) polymorphism and diabetic nephropathy

Congenic strains reveal the effect of the renin gene on skeletal muscle angiogenesis induced by electrical stimulation

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