Association between retinoid-X receptor-gamma genetic polymorphisms and diabetic retinopathy

Abstract

ABSTRACT. Retinoid-X receptor (RXR) is one of the members of the nuclear hormone receptor superfamily. It forms heterodimers with many nuclear receptors, such as the peroxisome proliferative-activated receptor, which has been proposed to be involved in diabetic complications, including retinopathy. A recent study revealed that RXR-alpha has antioxidant properties and is associated with diabetic retinopathy. We found that the RXR-gamma gene is involved in the pathogenesis of diabetic nephropathy. We also hypothesized that the RXR-gamma gene has a role in the development of diabetic retinopathy. We examined 213 diabetic patients, who were divided into retinopathy or no retinopathy groups. Nine selected single nucleotide polymorphisms (SNPs) in the RXR-gamma gene were evaluated. The diabetic retinopathy group had longer diabetes duration, higher body mass indexes, and higher systolic blood pressure, as well as higher concentrations of fasting plasma glucose, blood urine nitrogen, and creatine. One SNP -rs3818569 of the RXR-gamma gene was found to be associated with increased risk for diabetic retinopathy in both allele and genotype frequencies (P = 0.0023 and 0.0057, respectively). Analysis with multivariate logistic regression ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 10 (4): 3545-3551 (2011) C.-H. Hsieh et al. 3546 revealed that the dominant RXR-gamma GG genotype is a risk factors for the development of diabetic retinopathy (odds ratio = 2.388; 95% confidence interval = 1.17-4.875). We conclude that the RXR-gamma rs3818569 SNP is associated with diabetic retinopathy development in the Taiwanese population.

Associations between genetic variants and the severity of metabolic syndrome in subjects with type 2 diabetes

“…Our study presented 1 SNP (rs3818569, which was merged with rs1128977) in the RXRG gene, displaying a positive correlation with the development and severity of MetS with the GG genotype. Interestingly, this SNP is also involved in the development of diabetic nephropathy and retinopathy (Hsieh et al, 2011), indicating an important role in the development of diabetes-related traits sharing similar pathophysiological processes.…”

“…The detailed results have been published elsewhere (Hsieh et al, 2006(Hsieh et al, , 2011. Briefly, case and control groups of 264 patients with T2D, all ethnically Han Chinese, were recruited from the Tri-Service General Hospital in Taipei, Taiwan.…”

Genetic and environmental factors associated with type 2 diabetes and diabetic vascular complications

“…In the short term, the proportion of anti-VEGF-treated patients with complete regression of retinal neovascularization was significantly higher than in the control groups [124,125]. Polymorphism in the retinoid-X receptor (RXR) gamma gene has also been associated with DR (OR = 2.388; 95% confidence interval = 1.17-4.875) in Asians with T2D [126]. Polymorphisms in the regulatory region of the aldose reductase (ALR2) gene (encoding the rate-limiting enzyme of the polyol pathway) were associated with susceptibility to DN and DR [114,127].…”

Diabetic macular oedema: under‐represented in the genetic analysis of diabetic retinopathy

“…It can form heterodimers with several nuclear receptors, including peroxisome proliferator‐activated receptor (PPAR), and it has been shown to mediate the biological effects of several hormones and drugs (Mangelsdorf & Evans ; Hsieh et al. ). Through this mediation of lipid and glucose metabolism, RXR can have an impact on the development of diabetic complications.…”