The role of aldose reductase gene in the susceptibility to diabetic nephropathy in Type II (non-insulin-dependent) diabetes mellitus (Short Communication)

Moczulski, Dariusz; Burak, W; Doria, Alessandro; Zychma, Marcin; Żukowska-Szczechowska, E; Warram, James H.; Grzeszczak, W

doi:10.1007/s001250051119

Cited by 50 publications

(37 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our findings are in agreement with other reports (11)(12)(13)24,25) in China, Japan, and Chile that show associations between the z-2 allele and nephropathy and/or retinopathy in type 2 diabetic patients. However, two recent studies (26,27) reported a lack of association between the z-2 allele and microvascular complications in both type 1 and type 2 diabetic patients of Caucasian origin. This may be due to differences in ethnicity, study design, sample size, patient selection, and recruitment criteria.…”

Section: Discussionmentioning

confidence: 98%

Phenotypic Heterogeneity and Associations of Two Aldose Reductase Gene Polymorphisms With Nephropathy and Retinopathy in Type 2 Diabetes

Wang

Lee

et al. 2003

Diabetes Care

View full text Add to dashboard Cite

OBJECTIVE -We investigated the phenotypic features of diabetic microvascular complications and their association with a (CA) n microsatellite and a C/T polymorphism at the 5Ј region of the aldose reductase gene (ALR2) in a consecutive cohort of 738 Chinese type 2 diabetic patients.RESEARCH DESIGN AND METHODS -Of the entire patient cohort, 392 were free of diabetes complications, or uncomplicated, 159 had diabetic nephropathy, 66 had diabetic retinopathy, and 121 had both diabetic nephropathy and retinopathy. Nephropathy was defined as urinary albumin excretion rate (AER) Ն20 g/min and albumin-to-creatinine ratio Ն3.5 mg/ mmol in two urine collections. Retinopathy was defined by the presence of hemorrhages, exudates, laser marks, and fibrous proliferation or by a history of vitrectomy. (CA) n and C/T polymorphisms were examined by PCR followed by capillary electrophoresis and digestion with BfaI, respectively. RESULTS -In the whole cohort, patients with diabetic retinopathy (n ϭ 187) had higher blood pressure and lower BMI, while those with diabetic nephropathy (n ϭ 280) had higher blood pressure, waist-to-hip ratio, and lipid profile than those without the respective complications. The zϩ6 carriers of the (CA) n polymorphism were less common in patients with diabetic retinopathy than those without diabetic retinopathy (n ϭ 551) (4.3 vs. 9.3%, P ϭ 0.04). The CT/TT carriers had a higher AER than the CC carriers (30.2 ϫ/Ϭ 7.2 vs. 21.9 ϫ/Ϭ 6.9 g/min, P ϭ 0.03). Further subgroup analysis was performed after excluding uncomplicated patients with Ͻ5 years disease duration. The group with both diabetic nephropathy and retinopathy had higher frequencies of the z-2 allele (25.7 vs. 16.9%, P ϭ 0.03) and T allele (26.4 vs. 18.5%, P ϭ 0.04) and a lower frequency of the zϩ6 allele (1.7 vs. 5.5%, P ϭ 0.054) than the uncomplicated group. Multiple logistic regression analysis confirmed that z-2 carrying (odds ratio 2.6, 95% CI 1.20 -5.83, P ϭ 0.02) and CT/TT genotypes (OR 2.5, 95% CI 1.19 -5.19, P ϭ 0.02) were independent predictors for both diabetic nephropathy and retinopathy.CONCLUSIONS -Chinese type 2 diabetic patients exhibited phenotypic differences in terms of risk factors for both diabetic nephropathy and diabetic retinopathy. Both the z-2 allele of (CA) n polymorphism and T allele of ALR2 were independently associated with severe diabetic microvascular complications. Diabetes Care 26:2410 -2415, 2003G lycemic control, blood pressure, and disease duration are known predictive factors for the development of diabetic microvascular complications, including nephropathy and retinopathy (1,2). However, not all diabetic patients develop microvascular complications. Family studies in Pima Indian and Caucasian populations suggest genetic influences in the development of these complications (3,4). There is also increasing evidence (5,6) showing that non-Caucasian (including Asian) diabetic patients have a higher risk of renal complications than Caucasian populations. In Hong Kong, up to 50% of type 2 diabetic patients attending ho...

show abstract

Section: Discussionmentioning

confidence: 98%

Phenotypic Heterogeneity and Associations of Two Aldose Reductase Gene Polymorphisms With Nephropathy and Retinopathy in Type 2 Diabetes

Wang

Lee

et al. 2003

Diabetes Care

View full text Add to dashboard Cite

show abstract

“…The association was also observed in another Caucasian type 1 population [17], however it could not be confirmed by others [21, 22]. Most of the studies performed in type 2 diabetes did not show an association between diabetic nephropathy and the polymorphic (CA) n dinucleotide microsatellite [23,24,25]. …”

Section: Discussionmentioning

confidence: 81%

C-106T Polymorphism in Promoter of Aldose Reductase Gene Is a Risk Factor for Diabetic Nephropathy in Type 2 Diabetes Patients with Poor Glycaemic Control

Gosek¹,

Moczulski²,

Żukowska-Szczechowska³

et al. 2005

Nephron Exp Nephrol

View full text Add to dashboard Cite

Background: Excessive flux through the polyol pathway has long been thought to be involved in the pathogenesis of diabetic microvascular complications. Aldose reductase (AR) is the first and rate-limiting enzyme in the pathway that catalyses the reduction of glucose to sorbitol. A frequent C-106T polymorphism in the promoter of the AR gene has been described, which may change the expression of the gene. The aim of the study was to examine if the C-106T polymorphism was associated with diabetic nephropathy. Material and Methods: We collected 444 patients with type 2 diabetes and divided them into three groups according to the renal status: 162 patients with normoalbuminuria, 153 with microalbuminuria and 129 with persistent proteinuria. Each subject was genotyped for the C-106 polymorphism using the PCR-based RFLP protocol. Results: When the whole study population was analysed, no distortion in the genotype frequency among the study groups was observed. When we stratified the study population by HbA1c we found that in patients with HbA1c ≧9% (median) the CT and TT genotypes were more frequent in patients with diabetic nephropathy (proteinuria and microalbuminuria) than those with normoalbuminuria (OR 2.04, 95% CI 1.12–3.74). Conclusion: The C-106T polymorphism in the AR gene is a risk factor for development of diabetic nephropathy in type 2 diabetes in patients with poor glycaemic control.

show abstract

“…[43][44][45] A recent study, however, suggests that the aldose reductase gene may not play an important role in the susceptibility to diabetic nephropathy. 46 Affected sib-pair linkage analysis in the Pima Indians did not reveal any evidence of linkage on chromosome 17, the location of the ACE gene, 47 or on chromosome 1, the location for both the angiotensinogen gene 48 and the NHE-1 gene. 49 The AGTR1 gene maps on chromosome 3q21-q25, 50 approximately 20 cm from the marker that showed tentative evidence for linkage with diabetic nephropathy.…”

Section: Linkage Analysismentioning

confidence: 83%

Diabetic renal disease in transitional and disadvantaged populations

Weil

Nelson

2001

Nephrology

View full text Add to dashboard Cite

SUMMARY:Diabetes mellitus has reached epidemic proportions throughout much of the world, and people from developing countries and disadvantaged groups from developed countries are affected disproportionately. Not only is diabetes more common in these populations, but it develops at an earlier age. Accordingly, patients have more years of life in which to develop the chronic complications of diabetes and the risk of complications is often further enhanced by limited access to health care. Renal disease is a frequent consequence of diabetes in these populations, and a number of factors related to poverty, malnutrition and accelerated lifestyle changes may lead to even greater rates in the future.

show abstract

The role of aldose reductase gene in the susceptibility to diabetic nephropathy in Type II (non-insulin-dependent) diabetes mellitus (Short Communication)

Cited by 50 publications

References 11 publications

Phenotypic Heterogeneity and Associations of Two Aldose Reductase Gene Polymorphisms With Nephropathy and Retinopathy in Type 2 Diabetes

Phenotypic Heterogeneity and Associations of Two Aldose Reductase Gene Polymorphisms With Nephropathy and Retinopathy in Type 2 Diabetes

C-106T Polymorphism in Promoter of Aldose Reductase Gene Is a Risk Factor for Diabetic Nephropathy in Type 2 Diabetes Patients with Poor Glycaemic Control

Diabetic renal disease in transitional and disadvantaged populations

Contact Info

Product

Resources

About