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Aldose reductase (AC)n gene polymorphism in Iranian patients with type 2 diabetic microangiopathy; a case-control
Mohammad Bagher Hashemi-Soteh1, Ali Ahmadzadeh Amiri2, Majid Reza Sheikh Rezaee3
1Molecular and Cell Biology Department, Mazandaran University of Medical Sciences, Sari, Iran.
Aim:
(AC)n promoter region of the aldose reductase (ALR) genes polymorphism has been associated with diabetic microvascular complications (MVCs). The aim of this study was to find the relationship between dinucleotide repeat (AC)n polymorphisms of the ALR gene and the occurrence of MVCs, such as diabetic retinopathy, neuropathy, and nephropathy in Iranian type 2 diabetic (T2D) patients.
Methods:
This prospective case-control study was performed on T2D patients who were categorized into two groups based on the presence or absence of diabetic microangiopathy. All patients were provided informed consent. After extracting genomic DNA, the (AC)n of the ALR gene was determined using Polymerase chain reaction (PCR).
Results:
Thirteen alleles of the (AC)n gene polymorphism were detected including Z + 16, Z + 14, Z + 8, Z + 6, Z + 4, Z + 2, Z, Z - 2, Z - 4, Z - 6, Z - 8, Z - 10, and Z - 12. The frequency of the Z - 4 allele was significantly higher in patients with retinopathy, nephropathy, and autonomic neuropathy compared with those with long-term uncomplicated diabetes (P < 0.001, P < 0.001, P = 0.031, respectively). After controlling for baseline risk factors, we found that the carrier of the Z - 4 allele of ALR (AC)n polymorphism had a higher risk of diabetic retinopathy and diabetic nephropathy (P < 0.001). The homozygosity for the Z - 4 allele was found to be associated with diabetic microangiopathy.
Conclusion:
Our results showed that ALR (AC)n gene polymorphism in Iranian patients with type 2 diabetes independently, predispose retinal, renal and neural microvascular to diabetic complications.
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