Association study of HIF-1α rs11549465 and VEGF rs3025039 genetic variants with diabetic retinopathy in Egyptian patients: crosslinks with angiogenic, inflammatory, and anti-inflammatory markers

Mahmoud K Mohamed; Azza A Atef; Leqaa A Moemen; Amira A Abdel Azeem; Islam A Mohalhal; Alshaimaa M Taha

doi:10.1186/s43141-022-00401-9

Association study of HIF-1α rs11549465 and VEGF rs3025039 genetic variants with diabetic retinopathy in Egyptian patients: crosslinks with angiogenic, inflammatory, and anti-inflammatory markers

J Genet Eng Biotechnol. 2022 Aug 15;20(1):122. doi: 10.1186/s43141-022-00401-9.

Authors

Mahmoud K Mohamed¹, Azza A Atef², Leqaa A Moemen¹, Amira A Abdel Azeem³, Islam A Mohalhal⁴, Alshaimaa M Taha⁵

Affiliations

¹ Biochemistry Unit, Research Institute of Ophthalmology, Giza, Egypt.
² Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt.
³ Genetic ophthalmology, Research Institute of Ophthalmology, Giza, Egypt.
⁴ Surgical Retina, Research Institute of Ophthalmology, Giza, Egypt.
⁵ Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt. alshaimaa.taha@sci.asu.edu.eg.

Abstract

Background: Genetic factors are implicated in the progression of DR-a global cause of blindness. Hence, the current work investigated the association of HIF-1α rs11549465 and VEGF rs3025039 genetic variants with the different stages of retinopathy among T2DM Egyptian patients. The crosslinks of these variants were explored with angiogenesis (VEGF), inflammation (AGEP and VCAM-1), and anti-inflammation (CTRP3) markers. Two hundred eighty-eight subjects were recruited in this study: 72 served as controls and 216 were having T2DM and were divided into diabetics without retinopathy (DWR), diabetics with non-proliferative retinopathy (NPDR), and diabetics with proliferative retinopathy (PDR). The genetic variants were analyzed using PCR-RFLP and their associations with NPDR and PDR were statistically tested. The circulating levels of AGEP, VCAM-1, HIF-1α, VEGF, and CTRP3 were assayed followed by analyzing their associations statistically with the studied variants.

Results: Only HIF-1α rs11549465 genetic variant (recessive model) was significantly associated with the development of NPDR among T2DM patients (p < 0.025) with a significant correlation with the circulating HIF-1α level (p < 0.0001). However, this variant was not associated with PDR progression. Neither HIF-1α rs11549465 nor VEGF rs3025039 genetic variants were associated with the PDR progression. The circulating AGEP, VCAM-1, HIF-1α, and VEGF were significantly elevated (p < 0.0001) while the CTRP3 was significantly decreased (p < 0.0001) in NPDR and PDR groups. The HIF-1α rs11549465 CT and/or TT genotype carriers were significantly associated with AGEP and VCAM-1 levels in the NPDR group, while it showed a significant association with the CTRP3 level in the PDR group. The VEGF rs3025039 TT genotype carriers showed only a significant association with the CTRP3 level in the PDR group.

Conclusion: The significant association of HIF-1α rs11549465 other than VEGF rs3025039 with the initiation of NPDR in T2DM Egyptian patients might protect them from progression to the proliferative stage via elevating circulating HIF-1α. However, this protective role was not enough to prevent the development of NPDR because of enhancing angiogenesis and inflammation together with suppressing anti-inflammation. The non-significant association of HIF-1α rs11549465 with PDR among T2DM patients could not make this variant a risk factor for PDR progression.

Keywords: AGEP; CTRP3; NPDR; PDR; Risk factor; T2DM; VCAM-1; VEGF.