1. Long Non-Coding RNAs Gene Variants as Molecular Markers for Diabetic Retinopathy Risk and Response to Anti-VEGF Therapy
- Author
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Naglaa Mokhtar, Essam Al Ageeli, Ahmed A Abdelghany, Manal S. Fawzy, Ranya Hassan, Shahad W. Kattan, Hala M.F. Mohammad, and Eman A. Toraih
- Subjects
Oncology ,medicine.medical_specialty ,Type 2 diabetes ,Pharmacogenomics and Personalized Medicine ,Polymorphism (computer science) ,Internal medicine ,Genotype ,Medicine ,MALAT1 ,Genotyping ,Aflibercept ,Original Research ,Pharmacology ,SENCR ,business.industry ,aflibercept ,Diabetic retinopathy ,medicine.disease ,TUG1 ,MIAT ,diabetic retinopathy ,Molecular Medicine ,business ,Pharmacogenetics ,medicine.drug - Abstract
Background Long non-coding RNAs (lncRNAs) play essential roles in molecular diagnosis and therapeutic response in several diseases. Purpose For the first time, we aimed to evaluate the association of four lncRNAs TUG1 (rs7284767G/A), MIAT (rs1061540T/C), MALAT1 (rs3200401C/T), and SENCR (rs12420823C/T) variants with susceptibility to diabetic retinopathy (DR), disease severity, and early therapeutic response to intravitreous anti-vascular endothelial growth factor aflibercept therapy. Patients and Methods This case-control study enrolled 126 adult patients with type 2 diabetes. TaqMan assays using Real-Time PCR were run for genotyping. Multivariable regression analyses were applied to assess the role of each polymorphism after the adjustment of covariates. Results Carriers of TUG1 A/G and MIAT T/C and C/C genotypes were more likely to develop DR [OR=3.15 (95% CI=1.15–8.64), and OR=4.31 (95% CI=1.78–10.47)], while MALAT1 T/C conferred protection (OR=0.40, 95% CI=0.16–0.99). For TUG1, MALAT1, MIAT, and SENCR genotype combinations, GTCT and GCCC had a higher disease risk (P=0.012). For disease severity, MIAT T/T homozygosity was associated with higher DR grade [33.3% (T/T) vs 10% (C/C) and 4.2% (C/T) carriers, P=0.012]. Otherwise, patients with the SENCR T variant exhibited better pre-treatment best-corrected visual acuity level (p=0.021). Following aflibercept administration, carrying the TUG1 A or MIAT T/C was associated with a poor therapeutic response (OR=5.02, 95% CI=1.60–15.76, and OR=10.23, 95% CI=1.51–69.15, respectively). Conclusion The lncRNAs TUG1 (rs7284767G/A) and MIAT (rs1061540T/C) were associated with increased DR susceptibility and poor response to aflibercept treatment, while MALAT1 (rs3200401C/T) conferred protection to DR. These genetic determinants could be useful in DR risk stratification and pharmacogenetics after validation in large-scale studies., Graphical Abstract
- Published
- 2021