A Demaine1, D Cross, A Millward. 1. Department of Molecular Medicine, Plymouth Postgraduate Medical School, Tamar Science Park, Plymouth, United Kingdom. ademaine@plymouth.ac.uk
Abstract
PURPOSE: Aldose reductase (ALR2) is the first and rate-limiting enzyme of the polyol pathway and is involved in the pathogenesis of diabetic retinopathy. Polymorphisms of the ALR2 gene are associated with susceptibility to diabetic retinopathy in Chinese and Japanese patients with type 2 diabetes. There are no reports investigating these polymorphisms in white patients with type 1 diabetes from either Western Europe or North America. A CA dinucleotide repeat polymorphism (5'ALR2; located at -2100 bp) as well as a novel C(106)T polymorphism was investigated in 229 white patients with type 1 diabetes, with or without retinopathy. METHODS: The DNA was typed for these polymorphisms using conventional polymerase chain reaction techniques. RESULTS: There was a highly significant increase in the frequency of the Z-2 5'ALR2 allele and Z-2/X (where X is not Z+2) genotype in patients with diabetic retinopathy (n = 159) compared with those without who had diabetes of 20 years' duration (uncomplicated, n = 70; chi(2) = 17.0, P < 0.0001). There was a similar decrease in the Z+2/Y genotype (where Y is not Z-2; chi(2) = 30.1, P < 0.000,001) in the patients with retinopathy compared with the uncomplicated diabetes group. The C/Z-2 C(-106)T/5' ALR2 haplotype was found in 33.3% of the patients with retinopathy and 8.7% of the patients with uncomplicated diabetes. CONCLUSIONS: These results confirm previous studies in other populations and in type 2 diabetes showing that polymorphisms in the promoter region of the ALR2 gene are associated with susceptibility to diabetic retinopathy.
PURPOSE:Aldose reductase (ALR2) is the first and rate-limiting enzyme of the polyol pathway and is involved in the pathogenesis of diabetic retinopathy. Polymorphisms of the ALR2 gene are associated with susceptibility to diabetic retinopathy in Chinese and Japanese patients with type 2 diabetes. There are no reports investigating these polymorphisms in white patients with type 1 diabetes from either Western Europe or North America. A CA dinucleotide repeat polymorphism (5'ALR2; located at -2100 bp) as well as a novel C(106)T polymorphism was investigated in 229 white patients with type 1 diabetes, with or without retinopathy. METHODS: The DNA was typed for these polymorphisms using conventional polymerase chain reaction techniques. RESULTS: There was a highly significant increase in the frequency of the Z-2 5'ALR2 allele and Z-2/X (where X is not Z+2) genotype in patients with diabetic retinopathy (n = 159) compared with those without who had diabetes of 20 years' duration (uncomplicated, n = 70; chi(2) = 17.0, P < 0.0001). There was a similar decrease in the Z+2/Y genotype (where Y is not Z-2; chi(2) = 30.1, P < 0.000,001) in the patients with retinopathy compared with the uncomplicated diabetes group. The C/Z-2 C(-106)T/5' ALR2 haplotype was found in 33.3% of the patients with retinopathy and 8.7% of the patients with uncomplicated diabetes. CONCLUSIONS: These results confirm previous studies in other populations and in type 2 diabetes showing that polymorphisms in the promoter region of the ALR2 gene are associated with susceptibility to diabetic retinopathy.
Authors: Mohammad Bagher Hashemi-Soteh; Ali Ahmadzadeh Amiri; Majid Reza Sheikh Rezaee; Amir Ahmadzadeh Amiri; Soleiman Olfat; Ahmad Ahmadzadeh Amiri Journal: Diabetol Int Date: 2020-06-10
Authors: Flávio Richeti; Renata Maria Noronha; Ricardo Temudo Lessa Waetge; José Paulo Cabral de Vasconcellos; Osías Francisco de Souza; Bianca Kneipp; Nilma Assis; Mylene Neves Rocha; Luís Eduardo Procópio Calliari; Carlos Alberto Longui; Osmar Monte; Monica Barbosa de Melo Journal: Mol Vis Date: 2007-05-23 Impact factor: 2.367