Association of the rs9896052 Polymorphism Upstream of GRB2 with Proliferative Diabetic Retinopathy in Patients with Less than 10 Years of Diabetes

Growth factor receptor-bound protein 2 (GRB2) is a negative regulator of insulin signaling and a positive regulator of angiogenesis. Its expression is increased in a mouse model of retinal neovascularization and in patients with type 2 diabetes mellitus (T2DM). This case-control study aimed to inves...

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Published in:	International journal of molecular sciences Vol. 25; no. 19; p. 10232
Main Authors:	Bastos, Caroline Moura Cardoso, da Silva Machado, Lucas Marcelo, Crispim, Daisy, Canani, Luís Henrique, Dos Santos, Kátia Gonçalves
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI AG 01-10-2024 MDPI
Subjects:	Aged Angiogenesis Blood & organ donations Body mass index Brazil Case-Control Studies Cholesterol Communication Complications and side effects Cytokines Development and progression Diabetes Diabetes Mellitus, Type 2 - complications Diabetes Mellitus, Type 2 - genetics Diabetic retinopathy Diabetic Retinopathy - genetics Female Gene Frequency Genetic aspects genetic association Genetic Predisposition to Disease Genotype Genotype & phenotype GRB2 GRB2 Adaptor Protein - genetics Growth factors Health aspects Hemoglobin High density lipoprotein Humans Hyperglycemia Insulin Kinases Male Middle Aged Neovascularization Physiological aspects Polymorphism Polymorphism, Single Nucleotide Proteins Regression analysis Retina Risk factors rs9896052 Signal transduction Single nucleotide polymorphisms Skin Type 2 diabetes type 2 diabetes mellitus Brazil genetic association type 2 diabetes mellitus GRB2 polymorphism diabetic retinopathy rs9896052
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Summary:	Growth factor receptor-bound protein 2 (GRB2) is a negative regulator of insulin signaling and a positive regulator of angiogenesis. Its expression is increased in a mouse model of retinal neovascularization and in patients with type 2 diabetes mellitus (T2DM). This case-control study aimed to investigate the association between the rs9896052 polymorphism (A>C) upstream of and proliferative diabetic retinopathy (PDR) in patients with T2DM from Southern Brazil, taking into consideration self-reported skin color (white or non-white) and the known duration of diabetes (<10 years or ≥10 years). Genotypes were determined by real-time PCR in 838 patients with T2DM (284 cases with PDR and 554 controls without DR). In the total study group and in the analysis stratified by skin color, the genotype and allele frequencies were similar between cases and controls. However, among patients with less than 10 years of diabetes, the C allele was more frequent in cases than in controls (63.3% versus 51.8%, = 0.032), and the CC genotype was independently associated with an increased risk of PDR (adjusted OR = 2.82, 95% CI 1.17-6.75). In conclusion, our findings support the hypothesis that the rs9896052 polymorphism near is associated with PDR in Brazilian patients with T2DM.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1422-0067 1661-6596 1422-0067
DOI:	10.3390/ijms251910232