Mapping of Aldose Reductase Gene Sequences to Human Chromosomes 1, 3, 7, 9, 11, and 13

Jb, Bateman; T, Kojis; Heinzmann, C.; Klisak, I; Diep, Anh; Carper, Deborah; Nishimura, Chihiro; Mohandas, T.K.; Rs, Sparkes

doi:10.1006/geno.1993.1372

Cited by 10 publications

(5 citation statements)

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“…At about 1200 bp upstream of the transcription start site, there is a 132 basepair (bp) region containing three osmotic response elements: OreA, OreB and OreC 47. ALD2 pseudogenes have also been described 48.…”

Section: Polymorphisms Of Ald2 and Risk Of Diabetic Complicationmentioning

confidence: 99%

“…The “Z-2” (AC) n microsatellite polymorphism, i.e., (AC)23, has been associated with high expression levels of AR 56 and with rapid progression or increased prevalence of diabetic retinopathy 50, 54, diabetic nephropathy 55–58, and, less strongly, with diabetic neuropathy 58. In the last case, a relatively clear association was detected between microvascular complications and a decrease in the “protective,” low AR-expressing “Z+2” allele, i.e., (AC) 25 48. An equal 55 or even stronger 49 link with the C(-106)T promoter SNP has been found in several studies.…”

Section: Polymorphisms Of Ald2 and Risk Of Diabetic Complicationmentioning

confidence: 99%

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Aldose Reductase and Cardiovascular Diseases, Creating Human-Like Diabetic Complications in an Experimental Model

Ramasamy

Goldberg

2010

Circulation Research

135

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Hyperglycemia and reduced insulin actions affect many biological processes. One theory is that aberrant metabolism of glucose via several pathways including the polyol pathway causes cellular toxicity. Aldose reductase (AR) is a multifunctional enzyme that reduces aldehydes. Under diabetic conditions AR converts glucose into sorbitol, which is then converted to fructose. This article reviews the biology and pathobiology of AR actions. AR expression varies considerably among species. In humans and rats, the higher level of AR expression is associated with toxicity. Flux via AR is increased by ischemia and its inhibition during ischemia reperfusion reduces injury. However, similar pharmacological effects are not observed in mice unless they express a human AR transgene. This is because mice have much lower levels of AR expression, probably insufficient to generate toxic byproducts. Human AR expression in LDL receptor knockout mice exacerbates vascular disease, but only under diabetic conditions. In contrast, a recent report suggests that genetic ablation of AR increased atherosclerosis and increased hydroxynonenal in arteries. It was hypothesized that AR knockout prevented reduction of toxic aldehydes. Like many in vivo effects found in genetically manipulated animals, interpretation requires the reproduction of human-like physiology. For AR, this will require tissue specific expression of AR in sites and at levels that approximate those in humans. (Circ Res. 2010;106:1449-1458.)Key Words: diabetes Ⅲ macrovascular disease Ⅲ atherosclerosis Ⅲ fructose D uring the past decade, studies in genetically modified mice have been used to define processes that contribute to atherosclerosis. Alterations in macrophage and endothelial cell biology by genetic overexpression or deletion can greatly modify vascular lesion extent and also the composition of plaques; these latter effects are viewed as ways to uncover processes leading to plaque instability. Although many processes might alter inflammation and hence lesion extent and complexity, the observation that diabetes/hyperglycemia/ insulin-deficiency alone does not always result in greater Original received November 18, 2009; revision received April 7, 2010; accepted April 8, 2010. From the Departments of Surgery (R.R.) and Medicine (I.J.G.), Columbia University College of Physicians and Surgeons, New York. Correspondence to Dr Ravichandran Ramasamy, Department of Surgery, Columbia University, 630 West 168th St, Black Building 1706a, New York, NY 10032. E-mail rr260@columbia.edu © 2010 American Heart Association, Inc. Many genes are expressed in rodent tissues at levels that are disproportionate to those in humans, and these lead to changes in physiology and response to drugs that are totally different from those of humans. A case in point is the expression of peroxisome proliferator-activated receptor (PPAR) transcription factors. Rodent livers express much higher levels of both PPAR␣ and PPAR␥ than do humans. 2 For this reason, whereas activation of PPAR␣ in rats...

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Section: Polymorphisms Of Ald2 and Risk Of Diabetic Complicationmentioning

confidence: 99%

Section: Polymorphisms Of Ald2 and Risk Of Diabetic Complicationmentioning

confidence: 99%

Aldose Reductase and Cardiovascular Diseases, Creating Human-Like Diabetic Complications in an Experimental Model

Ramasamy

Goldberg

2010

Circulation Research

135

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“…Pseudogenes have also been found on chromosomes 1q35-q42, 3p12, 7q31-q35, 9q22, 11p14-p15, and 13q14-q21 [77]. The gene extends over 18 kilobases and contains 10 exons that code for a 1,384 base pair (bp) mRNA (excluding the poly A tail) [70].…”

Section: Polymorphisms Of the Aldose Reductase (Alr2) Genementioning

confidence: 99%

Polymorphisms of the Aldose Reductase Gene and Susceptibility to Diabetic Microvascular Complications

Ag¹

2003

CMC

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Diabetes is a major cause of mortality and morbidity due to the long term microvascular complications of this disease. There is now convincing evidence to show that genetic factors together with elevated blood glucose play an important role in the susceptibility to diabetic nephropathy as well as retinopathy. The polyol pathway is thought to play an important role in the pathogenesis of diabetic microvascular complications. Aldose reductase is the first and rate-limiting enzyme of the polyol pathway. Polymorphisms in the promoter region as well as elsewhere in the gene have been associated with susceptibility to nephropathy, retinopathy as well as diabetic neuropathy. These associations have been replicated in patients with either type 1 or type 2 diabetes mellitus as well as across ethnic groups. These polymorphisms in the promoter region are also associated with expression of the gene. Although clinical trials using inhibitors of aldose reductase to treat diabetic microvascular complications have largely been unsuccessful, the identification of the susceptibility genes may help in the design of future drug regimens.

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“…Chromosomal mapping (Graham et al, 1991b;Brown et al, 1992;Bateman et al, 1993) and the structure of AKR1B1 (Graham et al, 1991a) have been reported. The gene spans about 17 kb and consists of 10 exons.…”

Section: Discussionmentioning

confidence: 99%

“…By using a cDNA clone that encodes AKR1B1, the gene was mapped to human chromosomes 1q32→q42, 3p12, 7q31→q35, 9q22, 11p15 → p14, and 13q14 → q21 (Bateman et al, 1993). Graham et al (1991b) mapped the bona fide gene to chromosome region 7q35 using PCR in somatic cells, as well as in situ hybridization using a genomic clone as a probe.…”

Section: Discussionmentioning

confidence: 99%

The structural organization of the human aldehyde reductase gene, AKR1A1, and mapping to chromosome 1p33→p32

Fujii

Hamaoka²,

Matsumoto³

et al. 1999

Cytogenet Genome Res

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Mapping of Aldose Reductase Gene Sequences to Human Chromosomes 1, 3, 7, 9, 11, and 13

Cited by 10 publications

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Aldose Reductase and Cardiovascular Diseases, Creating Human-Like Diabetic Complications in an Experimental Model

Aldose Reductase and Cardiovascular Diseases, Creating Human-Like Diabetic Complications in an Experimental Model

Polymorphisms of the Aldose Reductase Gene and Susceptibility to Diabetic Microvascular Complications

The structural organization of the human aldehyde reductase gene, AKR1A1, and mapping to chromosome 1p33→p32

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