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

Aims  To investigate the association between polymorphisms of the aldose reductase gene and diabetic nephropathy in both Type 1 and Type 2 diabetes mellitus, and to carry out a meta‐analysis of published results. Methods  We have investigated the role of two aldose reductase polymorphisms in four in...

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Published in:Diabetic medicine 2001-11, Vol.18 (11), p.906-914
Main Authors: Neamat-Allah, M., Feeney, S. A., Savage, D. A., Maxwell, A. P., Hanson, R. L., Knowler, W. C., El Nahas, A. M., Plater, M. E., Shaw, J., Boulton, A. J. M., Duff, G. W., Cox, A.
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Aldehyde Reductase - genetics
aldose reductase
Alleles
Associated diseases and complications
Biological and medical sciences
Child
Diabetes Mellitus, Type 1 - genetics
Diabetes Mellitus, Type 2 - genetics
Diabetes. Impaired glucose tolerance
Diabetic Nephropathies - genetics
diabetic nephropathy
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Female
Gene Frequency
Genotype
Glycated Hemoglobin A - analysis
Humans
Linkage Disequilibrium
Male
Medical sciences
Microsatellite Repeats
Middle Aged
Odds Ratio
polymorphism
Polymorphism, Genetic
Type 1 diabetes
Type 2 diabetes
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Summary:Aims  To investigate the association between polymorphisms of the aldose reductase gene and diabetic nephropathy in both Type 1 and Type 2 diabetes mellitus, and to carry out a meta‐analysis of published results. Methods  We have investigated the role of two aldose reductase polymorphisms in four independent cohorts of cases and controls (two each with Type 1 and Type 2 diabetes) drawn from two ethnic populations, including 471 patients with nephropathy and 494 control diabetic patients without nephropathy. A C/T transition at position −106, and a (CA)n microsatellite marker 2.1 kb from the start site of the aldose reductase gene were genotyped in nephropathic patients and non‐nephropathic controls from each cohort. Results  Carriage of the −106 T allele was significantly associated with diabetic nephropathy in three of the four study groups. The Mantel‐Haenszel combined odds ratio was 2.22 (95% CI 1.69, 2.94), P = 1.05 × 10−8. We found no evidence for association of the microsatellite marker with nephropathy, despite moderate levels of disequilibrium between the two markers. Meta‐analysis of published data yielded no evidence for association of the microsatellite marker with diabetic nephropathy in Type 2 diabetes, but varying degrees of association with diabetic nephropathy in Type 1 diabetes. Conclusions  Meta‐analyses provide more convincing evidence of a role for the ALR2–106 marker than for the microsatellite marker in diabetic nephro pathy (DN). More studies are now required to confirm these results and to establish whether the ALR2–106 polymorphism has a functional role in DN. Diabet. Med. 18, 906–914 (2001)
ISSN:0742-3071
1464-5491
DOI:10.1046/j.0742-3071.2001.00598.x