Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. X:X | DOI: 10.5507/bp.2025.032

A case-control study of promoter and 5'UTR VEGF polymorphisms in diabetic retinopathy

Diala Walid Abu-Hassan¹, Muawyah D Al-Bdour^{2, 3, 4}, Huda Tahir¹, Mona Freihat^{2, 3, 4}, Ibraheem Saleh^{3, 5}, Mohammed El-Khateeb⁴, Mary J Kelley^{6, 7}

¹ Department of Physiology and Biochemistry, School of Medicine, The University of Jordan, Amman, Jordan

² Department of Ophthalmology, School of Medicine, The University of Jordan, Amman, Jordan

³ The Jordan University Hospital, Amman, Jordan

⁴ The National Center for Diabetes, Endocrinology and Genetics, Amman, Jordan

⁵ School of Medicine, The University of Jordan, Amman, Jordan

⁶ Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USA

⁷ Department Integrative Biosciences, School of Dentistry, Oregon Health & Science University, Portland, OR 97239, USA

Aims: Angiogenesis is activated in the retina of diabetic patients with retinopathy complications. Vascular endothelial growth factor (VEGF) plays an essential role as a mediator of the retinal induced neovascularization. VEGF levels are increased significantly in the vitreous and aqueous ocular fluids in the patients with proliferative diabetic retinopathy. The aim of this study is to investigate whether VEGF promoter/5'UTR polymorphisms are associated with diabetic retinopathy (DR) development and/or severity.

Methods: In this case-control study, Type 2 diabetic patients with or without DR, and normal controls were recruited. DR was classified based on the presence or absence of proliferative changes. The genotyping was analysed by polymerase chain reaction followed by restriction fragment length polymorphism.

Results: A total of 259 subjects (172 with diabetes+DR, 87 healthy controls; male:female, 125:134) were recruited. The average age was 59.5+9.6 years, diabetes duration was 8.5+4.5 years, body mass index was 30.6+6.0 kg/m2, and HbA1c was 7.37+1.2% (57 mmol/mol). Significant differences in the distribution of genotypes in T(-1,498)C, G(-1,190)A and G(-1,154)A polymorphism in diabetic patients versus controls, and DR patients versus DM without DR patients were shown. No association between DR severity and polymorphisms was detected. Non-significant differences in allele frequency were found. The haplotypes TGAGC, TGACT and CAGCT were significantly increased in DM patients, whereas CGGCC was the most common haplotype in DR patients.

Conclusions: Multiple VEGF polymorphisms and CGGCC haplotype are significantly correlated with a higher DR risk in Type 2 diabetic patients.

Keywords: angiogenesis, endothelial, ischemia, genetic, mutation, vascularization

Received: May 26, 2025; Revised: October 27, 2025; Accepted: November 24, 2025; Prepublished online: December 16, 2025