Genetic Variants in ICAM1, PPARGC1A and MTHFR Are Potentially Associated with Different Phenotypes of Diabetic Retinopathy

Abstract

Purpose: To explore phenotype-genotype correlations that may contribute to a better understanding of diabetic retinopathy (DR). Procedures: An exploratory association study was performed to identify genetic variants associated with non-proliferative DR (NPDR) in 307 type 2 diabetic patients who were previously stratified into 3 different phenotypes of NPDR progression. The 307 patients were genotyped for 174 single nucleotide polymorphisms of 11 candidate genes (ACE, AGER, AKR1B1, ICAM1, MTHFR, NOS1, NOS3, PPARGC1A, TGFB1, TNF and VEGFA). Results: Significant associations were observed for PPARGC1A rs16874120 with phenotype A (odds ratio, OR = 0.60, 95% confidence interval, CI 0.36-0.99), ICAM1 rs1801714 with phenotype B (OR = 3.32, 95% CI 1.05-10.50) and both PPARGC1A rs10213440 (OR = 2.00, 95% CI 1.07-3.73) and MTHFR rs1801133 (OR = 1.84, 95% CI 1.08-3.11) with phenotype C. Conclusions: Results indicate that specific gene variants in ICAM1, PPARGC1A and MTHFR are associated with different NPDR phenotypes, being likely candidates to explain different disease mechanisms underlying the different phenotypes. This is the first study to show correlations between specific gene variants and NPDR phenotypes, opening new perspectives on DR.

Diabetic Retinopathy: Need for More Research to Understand the Relative Role of Neuropathy and Microvascular Disease

“…Preliminary results support the concept that the occurrence and progression of microvascular disease are related to genetic factors [13] and may be independent of the diabetic retinal neuropathy. Heritability has, indeed, been estimated to be as high as 27% for DR and 52% for proliferative DR [14] .…”

A genome‐wide association study suggests new evidence for an association of the NADPH Oxidase 4 (NOX4) gene with severe diabetic retinopathy in type 2 diabetes

“…Genome-wide linkage studies have proposed multiple chromosome loci to be linked with DR using multiple ethnic groups, while no specific genes have been identified (Looker et al 2007; Hallman et al 2007; Imperatore et al 1998). Candidate gene approaches have suggested promising genes with possible biological connections with DR such as VEGFA , AKR1B1 , AGER , ICAM1 , MTHFR while larger samples will be required to further consolidate the reliability of these results (Awata et al 2002; Lindholm et al 2006; Abhary et al 2010; Simoes et al 2014; Opatrilova et al 2017). …”

A Meta-Analysis of Association between Methylenetetrahydrofolate Reductase Gene (MTHFR) 677C/T Polymorphism and Diabetic Retinopathy

“…In addition, 52 articles were excluded based on a review of the titles and abstracts, and 20 full-text articles were assessed for eligibility; 2 articles were excluded due to could not provide each genotype frequency or other sufficient information for extraction of data. Finally, a total of 18 [12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29] articles were included in this meta-analysis.…”

“…Numerous molecular epidemiological studies have been performed to estimate the relationship between the MTHFR 677C/T polymorphism and DR [12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29], but the results remain inconclusive. Although several meta-analyses have been published [30,31], they still did not reach a consistent conclusion.…”