Meta‑analysis of the association between aldose reductase gene (CA)n microsatellite variants and risk of diabetic retinopathy

Abstract

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.

Identifying Genetic Risk Factors for Diabetic Macular Edema and the Response to Treatment

“…These allelic polymorphisms have been hypothesized to alter ALR2 mRNA levels and hence enzyme activity, thus contributing to diabetic microvascular complications [ 56 ]. However, to date, conflicting evidence has been presented; some studies have reported an association between the Z-2 allele and DR risk [ 57 , 58 ], whereas others have reported no association [ 54 , 55 ]. In a meta-analysis by Mi et al [ 57 ], comprising 17 studies, the Z-2 allele was reported as a risk polymorphism for DR in both Asian and Caucasian T1 and T2DM cohorts.…”

“…However, to date, conflicting evidence has been presented; some studies have reported an association between the Z-2 allele and DR risk [ 57 , 58 ], whereas others have reported no association [ 54 , 55 ]. In a meta-analysis by Mi et al [ 57 ], comprising 17 studies, the Z-2 allele was reported as a risk polymorphism for DR in both Asian and Caucasian T1 and T2DM cohorts. Notably, only one study by Kumaramanickavel et al [ 59 ] has explored the association between the ALR2 dinucleotide repeat and DME risk.…”

Genetics of Diabetic Retinopathy, a Leading Cause of Irreversible Blindness in the Industrialized World

“…Some studies have suggested that the z-2 allele is associated with increased ALR activity [67] and DR pathogenesis in both T2D (stronger association) and T1D (weaker association) patients [50,53,68,69]. Two large meta-analyses have confirmed these findings, and both additionally found that the z+2 allele may be significantly protective against DR development in T2D [26,70]. Notably, however, found no significant association between any (CA)n allele and T2D once established risk factors were controlled for [30], suggesting that the (CA)n microsatellite may be only secondarily associated with DR through other clinical risk factors, rather than playing a primary role in its pathogenesis.…”

Review of the correlation between Chinese medicine and intestinal microbiota on the efficacy of diabetes mellitus

“…Insulin resistance (IR) and impaired islet cell functions are characterized by an increase in glycemia, lipid metabolism disorders, and systemic inflammation that can lead to a variety of serious complications ( 1 ). According to the World Health Organization, diabetes is one of the diseases with the most known complications ( 2 , 3 ). Long-term increases in blood glucose are accompanied by large blood vessels and microvascular damage, putting the heart, brain, kidneys, peripheral nerves, eyes, feet, and other organs at risk.…”

“…complications (1). According to the World Health Organization, diabetes is one of the diseases with the most known complications (2,3). Long-term increases in blood glucose are accompanied by large blood vessels and microvascular damage, putting the heart, brain, kidneys, peripheral nerves, eyes, feet, and other organs at risk.…”