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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

2001; Wiley; Volume: 18; Issue: 11 Linguagem: Inglês

10.1046/j.0742-3071.2001.00598.x

1464-5491

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

Alcohol Consumption and Health Effects

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)