Received: 07.07.2022; Accepted: 17.08.2022; Published on-line: 27.10.2022
Role of polymorphisms of folate-cycle enzymes in diabetic retinopathy progression in patients with type 2 diabetic mellitus
S. O. Rykov 1, Iu. V. Prokopenko 1, L. V. Natrus 2, Iu. O. Panchenko 1
1 Shupyk National Healthcare University of Ukraine
2 Bogomolets national medical university
TO CITE THIS ARTICLE: Rykov SO, Prokopenko IuV, Natrus LV, Panchenko IuO. Role of polymorphisms of folate-cycle enzymes in diabetic retinopathy progression in patients with type 2 diabetic mellitus. J.ophthalmol.(Ukraine).2022;5:3-11. http://doi.org/10.31288/oftalmolzh20225311
Background: Hyperhomocysteinemia is important in the development of endothelial dysfunction, a pathogenetic component of diabetic retinopathy (DR) in type 2 diabetes mellitus (DM2). The major cause of homocysteine accumulation is missing or dysfunctional enzymes and cofactors that are needed to perform homocystein metabolic processes. This is, for the most part, the deficiency of folate cycle enzymes determined by methylenetetrahydrofolate reductase (MTHFR) C677T, MTHFR A1298C, and methionine synthase (MTR) A2756G polymorphisms.
Purpose: To assess the role of polymorphisms of folate cycle enzymes (MTHFR C677T, MTHFR A1298C, MTR A2756G) in DR progression in patients with DM2.
Material and Methods: The study included 83 DM2 patients (83 eyes) in whom DR met the criteria of non-proliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR) according to the Early Treatment of Diabetic Retinopathy Study (ETDRS). The control group was composed of 35 non-diabetics comparable to patients with respect to gender, age and body mass index. Real-time PCR was conducted on a Gene Amp® PCR System 7500 to determine polymorphisms. Plasma L-homocysteine levels were determined using an enzyme-linked immunosorbent assay (ELISA) microplate reader and Axis® Homocysteine Enzyme Immunoassay Kit (AXIS-SHIELD Diagnostics Ltd).
Conclusion: We found no association of rs1801133, rs1805087, and rs1801131, folate-cycle polymorphisms, with the development of DR in DM2, compared with non-diabetics. In NPDR patients having the minor homozygous GG genotype of MTR 2756А/G and/or the minor homozygous CC genotype of MTHFR 1298A/C, plasma L-homocysteine levels were significantly increased. This requires further elucidation of the role of hyperhomocysteinemia as a factor of DR progression or as a marker of the severity of tissue injury. The duration of DM2 is an important factor of DR progression in carriers of the most common CC and CT genotypes of rs1801133, AG genotype of rs1805087, and АА genotype of rs1801131.
Keywords: diabetic retinopathy, type 2 diabetes mellitus, folate cycle, homocystein, MTHFR C677T, MTHFR A1298C, MTRA 2756G polymorphisms
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Corresponding Author: Larysa Natrus, e-mail: firstname.lastname@example.org
Authour Contribution: All authors meet the criteria of authorship, certify that each author has substantially contributed to the work, including conception, design, analysis, writing and revision of the article, and each author is responsible for its content.
Sources of Support: There are no external sources of funding.
Conflict of Interest Statement: All authors have no real or potential conflicts of interest (financial, personal, professional, or other) that could affect the subject matter or material described and discussed in this manuscript.
Sources of support: There are no external sources of funding.
Study Participants: All participants gave informed consent to participate in the study. The study was conducted in compliance with the requirements of the Declaration of Helsinki, the Council of Europe Convention on Human Rights and Biomedicine (1977), the relevant provisions of the WHO, the International Council of Medical Scientific Societies, the International Code of Medical Ethics (1983) and the Order of the Ministry of Health of Ukraine № 690 of 23.09.2009.