Pharmacogenomics and Personalized Medicine (Aug 2021)

Long Non-Coding RNAs Gene Variants as Molecular Markers for Diabetic Retinopathy Risk and Response to Anti-VEGF Therapy

  • Mohammad HMF,
  • Abdelghany AA,
  • Al Ageeli E,
  • Kattan SW,
  • Hassan R,
  • Toraih EA,
  • Fawzy MS,
  • Mokhtar N

Journal volume & issue
Vol. Volume 14
pp. 997 – 1014

Abstract

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Hala MF Mohammad,1,2 Ahmed A Abdelghany,3 Essam Al Ageeli,4 Shahad W Kattan,5 Ranya Hassan,6 Eman A Toraih,7,8 Manal S Fawzy,9,10 Naglaa Mokhtar10,11 1Department of Clinical Pharmacology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt; 2Central Laboratory, Center of Excellence in Molecular and Cellular Medicine (CEMCM), Faculty of Medicine, Suez Canal University, Ismailia, Egypt; 3Department of Ophthalmology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt; 4Department of Clinical Biochemistry (Medical Genetics), Faculty of Medicine, Jazan University, Jazan, Saudi Arabia; 5Department of Medical Laboratory, College of Applied Medical Sciences, Taibah University, Yanbu, Saudi Arabia; 6Department of Clinical Pathology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt; 7Department of Surgery, Tulane University, School of Medicine, New Orleans, LA, USA; 8Genetics Unit, Department of Histology and Cell Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt; 9Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt; 10Department of Biochemistry, Faculty of Medicine, Northern Border University, Arar, Saudi Arabia; 11Department of Medical Biochemistry, Faculty of Medicine, Mansoura University, Mansoura, EgyptCorrespondence: Manal S FawzyDepartment of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Suez Canal University, Ismailia, 41522, EgyptTel + 20 1008584720Fax + 20 64 321 6496Email [email protected]: 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.Keywords: aflibercept, diabetic retinopathy, MALAT1, MIAT, SENCR, TUG1

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