Analysis of the association between diabetic nephropathy and polymorphisms in the aldose reductase gene in Type 1 and Type 2 diabetes mellitus

Neamatallah, Mustafa; Feeney, Susan; Savage, David A.; Maxwell, Alexander P.; Hanson, Robert L.; Knowler, William C.; Nahas, A. Meguid El; Plater, M. E.; Shaw, Jonathan E.; Boulton, Andrew J.M.; Duff, Gordon W.; Cox, Angela

doi:10.1046/j.0742-3071.2001.00598.x

Cited by 47 publications

(48 citation statements)

References 35 publications

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“…A second polymorphism in this gene has been observed at position-106 of its promoter region. This polymorphism in aldose reductase gene was also found to be associated with nephropathy in type 1 and type 2 diabetic patients [54] . This polymorphism was also found to be involved in the early development of microalbuminuria in Finnish T2DM patients and was proposed as a risk factor for development of nephropathy in T2DM patients with poor glycaemic control [55] .…”

Section: Resultsmentioning

confidence: 99%

Association of genetic variants with diabetic nephropathy

Rizvi

Raza

Mahdi

2014

WJD

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Section: Resultsmentioning

confidence: 99%

Association of genetic variants with diabetic nephropathy

Rizvi

Raza

Mahdi

2014

WJD

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“…As noted above, three genes for which our results are negative (ACE, AKR1B1, and APOE) have been the subject of many studies of association in diabetic nephropathy, so we comment further here. The variants tested were as follows: 1) the 287-bp insertion/deletion (in/del) polymorphism in intron 16 of ACE (37)(38)(39)(40)(41)(42)(43)(44), 2) the CA-repeat STRP at AKR1B1 (45)(46)(47)(48)(49)(50)(51), and 3) the APOE polymorphism (25,(52)(53)(54)(55)(56). In our results (Table 4), we see a trend that supports these findings, but our sample size is small, and results are mostly not significant: ACE in/del (deletion allele, 38:31 transmissions:nontransmissions, 55.1% transmissions in the TDT analysis, P Ͼ 0.5); AKR1B1 5ЈCA-repeat polymorphism (ZϪ2 allele, 27:22, 55.1% transmissions, P Ͼ 0.5; Zϩ2 allele, 8:15, 34.8% transmissions, P Ͼ 0.5); and APOE (e2 "risk" allele, 12:2, 85.7% transmissions, P ϭ 0.008).…”

Section: Hnf1b1/transcription Factor 2 Hepatic (Mody5)mentioning

confidence: 99%

Assessment of 115 Candidate Genes for Diabetic Nephropathy by Transmission/Disequilibrium Test

et al. 2005

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Several lines of evidence, including familial aggregation, suggest that allelic variation contributes to risk of diabetic nephropathy. To assess the evidence for specific susceptibility genes, we used the transmission/disequilibrium test (TDT) to analyze 115 candidate genes for linkage and association with diabetic nephropathy. A comprehensive survey of this sort has not been undertaken before. Single nucleotide polymorphisms and simple tandem repeat polymorphisms located within 10 kb of the candidate genes were genotyped in a total of 72 type 1 diabetic families of European descent. All families had at least one offspring with diabetes and end-stage renal disease or proteinuria. As a consequence of the large number of statistical tests and modest P values, findings for some genes may be false-positives. Furthermore, the small sample size resulted in limited power, so the effects of some tested genes may not be detectable, even if they contribute to susceptibility. Nevertheless, nominally significant TDT results (P < 0.05) were obtained with polymorphisms in 20 genes, including 12 that have not been studied previously: aquaporin 1; B-cell leukemia/lymphoma 2 (bcl-2) protooncogene; catalase; glutathione peroxidase 1; IGF1; laminin alpha 4; laminin, gamma 1; SMAD, mothers against DPP homolog 3; transforming growth factor, beta receptor II; transforming growth factor, beta receptor III; tissue inhibitor of metalloproteinase 3; and upstream transcription factor 1. In addition, our results provide modest support for a number of candidate genes previously studied by others. Diabetes 54:3305-3318, 2005 D iabetic nephropathy is the most serious longterm complication of diabetes, accounting for ϳ40% of new cases of end-stage renal disease (ESRD) in the U.S. (1). Two lines of evidence suggest a strong genetic component in susceptibility to diabetic kidney disease. 1) Epidemiological studies indicate that the prevalence of diabetic nephropathy increases during the first 15-20 years after onset of diabetes and then reaches a plateau, suggesting that only a subset of patients is susceptible to the development of kidney disease (2). 2) Family studies show clustering of diabetic nephropathy in both type 1 and type 2 diabetes; diabetic siblings of probands with diabetic nephropathy have a significantly greater risk for developing kidney complications than diabetic siblings of probands without diabetic nephropathy (3-6). In addition, segregation analyses of diabetic nephropathy in both Caucasians and Pima Indians with type 2 diabetes provide evidence for the presence of a major locus, with a possible role for several minor loci (7,8).Numerous metabolic pathways and associated groups of genes have been proposed as candidates to play a role in the genetic susceptibility to diabetic nephropathy (9 -12). Before onset of overt proteinuria, functional changes are observed in the kidney (altered glomerular filtration rates and increasing albumin excretion rates), which are thought to result from the underlying pathological changes that...

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“…In type 2 diabetes, only 33% of patients with microalbuminuria have classic diabetic glomerulopathy (7,8). The histopathologic heterogeneity of nephropathy in type 2 diabetes may account for the controversial findings regarding the 5Ј-(CA) n polymorphism of the aldose reductase gene (28,29,33). In type 1 diabetes, the structural basis for nephropathy is usually the classic diabetic glomerulopathy, as reflected by mesangial expansion and basement membrane thickening (49).…”

Section: Discussionmentioning

confidence: 99%

Association of Glomerulopathy With the 5′-End Polymorphism of the Aldose Reductase Gene and Renal Insufficiency in Type 2 Diabetic Patients

et al. 2004

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The expression of nephropathy in type 2 diabetes has several levels of abnormalities. To define the primary abnormalities of diabetic nephropathy, we conducted an autopsy study of 186 consecutive patients with type 2 diabetes to determine correlations among the aldose reductase gene, renal histopathologies, extracellular matrix, glomerular function, and clinical characteristics. Compared with cases of near-normal renal structure (n ‫؍‬ 51) and atypical diabetic glomerulopathy (n ‫؍‬ 75), patients with classic diabetic glomerulopathy (n ‫؍‬ 60) had advanced glomerular disease, as reflected by elevated plasma creatinine levels (133.2 ؎ 59.8 vs.

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Analysis of the association between diabetic nephropathy and polymorphisms in the aldose reductase gene in Type 1 and Type 2 diabetes mellitus

Abstract: Meta-analyses provide more convincing evidence of a role for the ALR2-106 marker than for the microsatellite marker in diabetic nephropathy (DN). More studies are now required to confirm these results and to establish whether the ALR2-106 polymorphism has a functional role in DN.

Cited by 47 publications

References 35 publications

Association of genetic variants with diabetic nephropathy

Association of genetic variants with diabetic nephropathy

Assessment of 115 Candidate Genes for Diabetic Nephropathy by Transmission/Disequilibrium Test

Association of Glomerulopathy With the 5′-End Polymorphism of the Aldose Reductase Gene and Renal Insufficiency in Type 2 Diabetic Patients

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