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Interaction Between Genetic Polymorphisms in Renin-Angiotensin System (RAS) and Therapeutic Efficacy of RAS Blockade in IgA Nephropathy

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Blockade of the renin-angiotensin system (RAS), such as angiotensin-converting enzyme inhibitor and / or angiotensin receptor blocker, has been well appreciated as a renoprotective treatment in proteinuric glomerular diseases. However, not all patients with glomerular diseases respond well to this therapy. It would be important to predict the renoprotective effects of anti-hypertensive agents for individual patients with renal disease. The inter-individual variation in responsiveness to RAS blockade has been suggested to be in part genetically determined, whereas the results of previous reports, which mainly tested the interaction between the efficacy of angiotensin-converting enzyme (ACE) inhibitors and ACE insertion / deletion (I / D) polymorphism, have been conflicting in both diabetic and non-diabetic renal diseases. Some of the recent progress in human genome science can be applied to these problems. In particular, single nucleotide polymorphism of A2350G, an ACE gene variation other than the I / D polymorphism, which has a stronger association with the circulating level of ACE, has been shown to be a candidate marker for responsiveness to RAS blockade. In addition, angiotensinogen gene polymorphisms may also be involved in the inter-individual difference in the responsiveness to the renoprotective efficacy of the RAS blockade.

This review focuses on the interface between genomics and therapeutics in the renin-angiotensin system in IgAN, which is the most prevalent form of primary glomerulonephritis and one of the major causes of end-stage renal disease in the world.
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Keywords: Iga nephropathy; ace insertion; genetic polymorphisms; ras blockade; renin-angiotensin system

Document Type: Review Article

Affiliations: Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757, Asahimachi-dori, Niigata, 951-8510, Japan.

Publication date: June 1, 2004

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  • Current Pharmacogenomics provides comprehensive overviews of all current research on pharmacogenomics and pharmacogenetics. All areas of the field from pre-clinical to clinical research are covered, including related areas such as genomics, proteomics, target discovery, bioinformatics and novel diagnostics. This international journal is peer-reviewed and publishes both mini- and full review articles.

    The journal has become essential reading for all researchers and clinicians with interests in pharmacogenomics and pharmacogenetics.
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