Abstract
BackgroundGenetic association of uncoupling proteins (UCPs) variants with the susceptibility of diabetic retinopathy (DR) in diabetes mellitus (DM) patients has been reported but with controversy. Here we aimed to conduct a meta-analysis to confirm the association of different UCPs variants with DR.MethodsThree databases (Medline Ovid, Embase Ovid and CENTRAL) were applied in the literature search. Five genetic models, including allelic, homozygous, heterozygous, dominant and recessive models, were evaluated. Odds ratios (OR) were estimated under the random or fixed-effects models. Subgroup analyses, publication bias and sensitivity analyses were also conducted.ResultsEleven studies on 2 UCPs variants (UCP1 rs1800592 and UCP2 rs659366) were included. Our meta-analysis showed that UCP1 rs1800592 was not associated with DR in type-2 DM patients, and UCP2 rs659366 also showed no association with DR. In the subgroup analyses on the stage of DR, allele G of UCP1 rs1800592 significantly increased the susceptibility of proliferative diabetic retinopathy (PDR) in type-2 DM patients in the allelic (OR = 1.26, P = 0.03) and homozygous models (OR = 1.60, P = 0.04). Subgroup analysis on ethnicity did not found any significant association of rs1800592 and rs659366 with DR.ConclusionOur meta-analysis confirmed the association of UCP1 rs1800592 variant with PDR in patients with type-2 DM, suggesting its potential as a genetic marker for PDR prediction in population screening.
Highlights
Genetic association of uncoupling proteins (UCPs) variants with the susceptibility of diabetic retinopathy (DR) in diabetes mellitus (DM) patients has been reported but with controversy
The elevation of oxidative stress has been suggested contributing to the development of DM complications [5], which is caused by reactive oxygen species (ROS) overproduction, mainly the mitochondrial ROS [5,6,7]
Our results showed that Uncoupling protein 1 (UCP1) rs1800592 variant was not significantly associated with DR in type-2 DM patients in the pooled effects analysis (Table 3 and Fig. 2); yet, in the subgroup analysis, UCP1 rs1800592 was significantly associated with proliferative diabetic retinopathy (PDR) in type-2 DM patients in the allelic and homozygous models (Table 4 and Fig. 4)
Summary
Genetic association of uncoupling proteins (UCPs) variants with the susceptibility of diabetic retinopathy (DR) in diabetes mellitus (DM) patients has been reported but with controversy. The elevation of oxidative stress has been suggested contributing to the development of DM complications [5], which is caused by reactive oxygen species (ROS) overproduction, mainly the mitochondrial ROS [5,6,7]. UCPs are able to uncouple the oxidized substrates and dissipate the potential energy on the inner membrane as heat to reduce ROS overproduction from mitochondria [14,15,16,17]. Uncoupling protein 1 (UCP1) gene is located on chromosome 4q31.1 and found to be expressed in brown adipose tissue, endothelial cells and pericytes of retina [20]. UCP2 and UCP3, together with SLC25A27 (UCP4) and BMCP1 (UCP5), exert cytoprotective effects by reducing oxidative stress under certain conditions [22]
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