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

  1. M. Neamat-Allah1,
  2. S. A. Feeney2,
  3. D. A. Savage2,
  4. A. P. Maxwell3,
  5. R. L. Hanson4,
  6. W. C. Knowler4,
  7. A. M. El Nahas5,
  8. M. E. Plater6,
  9. J. Shaw7,
  10. A. J. M. Boulton7,
  11. G. W. Duff1,
  12. A. Cox1,3

Article first published online: 20 DEC 2001

DOI: 10.1046/j.0742-3071.2001.00598.x

Issue

Diabetic Medicine

Diabetic Medicine

Volume 18, Issue 11, pages 906–914, November 2001

Additional Information

How to Cite

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. and Cox, A. (2001), Analysis of the association between diabetic nephropathy and polymorphisms in the aldose reductase gene in Type 1 and Type 2 diabetes mellitus. Diabetic Medicine, 18: 906–914. doi: 10.1046/j.0742-3071.2001.00598.x

Author Information

  1. 1

    Division of Molecular and Genetic Medicine, University of Sheffield, Sheffield, UK,

  2. 2

    Department of Medical Genetics, Queen's University Belfast, Belfast, UK,

  3. 3

    Regional Nephrology Unit, Belfast City Hospital, Belfast, UK,

  4. 4

    NIDDK, NIH, Phoenix, Arizona, USA,

  5. 5

    Sheffield Kidney Institute, Northern General Hospital, Sheffield, UK,

  6. 6

    Diabetes Unit, Royal Hallamshire Hospital, Sheffield, UK,

  7. 7

    Manchester Royal Infirmary, Manchester, UK

* Angela Cox, Institute for Cancer Studies, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK. E-mail: a.cox@sheffield.ac.uk

Publication History

  1. Issue published online: 20 DEC 2001
  2. Article first published online: 20 DEC 2001
  3. Accepted 16 May 2001

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Keywords:

  • aldose reductase;
  • polymorphism;
  • Type 1 diabetes;
  • Type 2 diabetes;
  • diabetic nephropathy

Abstract

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)

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