Dataset Information

The relationship between aldose reductase gene C106T polymorphism and the severity of retinopathy in Type 2 diabetic patients: A case-control study.

ABSTRACT:

Background

Hyperglycemia over-activates glucose reduction to sorbitol by aldose reductase (ALR) leading to osmoregulation disruption and cellular damage that cause diabetic complications. We investigated the association of C106T polymorphism of ALR2 gene with the severity of diabetic retinopathy (DR) in Jordanian Type 2 diabetic patients in this case-control study at the Ophthalmology clinic of the National Centre of Diabetes, Endocrinology, and Genetics.

Materials and methods

A total of 277 subjects participated in the study (100 diabetics without retinopathy, 82 diabetics with retinopathy, and 95 controls). Blood samples were withdrawn followed by DNA extraction. C106T polymorphism was examined by polymerase chain reaction followed by restriction fragment length polymorphism and gel electrophoresis. Statistical analysis was performed by SPSS software using analysis of variance, multiple logistic regression or Chi-square test.

Results

The CT and TT genotypes were significantly more prevalent in DR patients than those without DR (CT 50% vs. 38%, TT 16.7% vs. 8%, P = 0.02 and 0.01, respectively). DR patients had T allele more frequently than those without it (41.7% vs. 27%, P = 0.007). Diabetics without retinopathy showed similar genotype and allele frequency to those of nondiabetic controls. No correlation between CT/TT genotypes and the severity of DR in affected subjects was found (χ²: 3.049, P = 0.550).

Conclusion

C106T polymorphism increased the risk to develop retinopathy in Jordanian Type 2 diabetic patients. T allele of ALR2 was associated with DR. The severity of DR did not show an association with this polymorphism.

SUBMITTER: Abu-Hassan DW

PROVIDER: S-EPMC8103958 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Diabetic retinopathy (DR) is one of the most severe microvascular complications of diabetes mellitus (DM). The (CA)n microsatellite variation of the aldose reductase (ALR) gene has been indicated to be associated with DR in previous studies; however, the results were inconclusive. To provide a more precise evaluation of the association between the (CA)n variations of ALR and the risk for DR, a meta-analysis was performed in the present study. Relevant articles were retrieved from the PubMed, Embase, Chinese National Knowledge Infrastructure and Cochrane Library databases. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of the associations. The present meta-analysis included 17 studies comprising 1,575 DM patients with retinopathy and 1,741 DM patients without retinopathy. The results indicated that the Z-2 allele was a risk factor for DR in Asian (OR=1.82, 95% CI: 1.16-2.86, P=0.009) and Caucasian (OR=2.08, 95% CI: 1.14-3.79, P=0.02) populations, as well as in type 1 diabetes (T1D; OR=3.42, 95% CI: 1.46-8.04, P=0.005) and type 2 diabetes (T2D; OR=1.66, 95% CI: 1.05-2.63, P=0.03). Furthermore, the Z+2 allele was determined to be a protective factor for DR in Caucasian individuals (OR=0.50, 95% CI: 0.34-0.73, P=0.0004) and those with T1D (OR=0.39, 95% CI: 0.27-0.57, P<0.00001). Z+4 was also identified to be a protective factor, reducing the risk of DR in patients with T1D (OR=0.74, 95% CI: 0.57-0.96, P=0.02). Z-4 was revealed to be a risk factor for DR in Asian populations (OR=1.57, 95% CI: 1.22-2.03, P=0.0005) and in individuals with T1D (OR=1.62, 95% CI: 1.27-2.08, P=0.0001). However, no association was detected between the Z, Z+6 and Z-6 alleles and the risk of DR (P>0.05). In conclusion, the present results revealed the following: Z+2 may serve as a protective factor for DR in Caucasian individuals and those with T1D; Z+4 may be a protective factor for DR in patients with T2D; Z-2 may represent a risk factor for DR in all subgroups analyzed; and Z-4 may be a risk factor for DR in Asian populations and patients with T2D.