Possible role of the TGFB1 polymorphism rs1800470, trophoblastic growth factor β1 (TGF-β1) and connective tissue growth factor (CTGF) in the progression of diabetic retinopathy in type 2 diabetes mellitus.

Aim: To determine the significance of growth factors (TGF-β1 and CTGF) in the development and progression of diabetic retinopathy (DR) in carriers of different genotypes of the TGFB1 rs1800470 polymorphism in type 2 diabetes mellitus (T2DM).

Materials and Methods: 102 individuals with T2DM and DR were examined, who were divided into 3 groups: 1st – with non-proliferative DR (NPDR, 35 individuals), 2nd – with preproliferative (PPDR, 34 individuals) and 3rd – with proliferative (PDR,33 individuals); 61 individuals were included in the control group. The patients underwent standard ophthalmological examinations. Determination of TGF-β1 in blood serum and intraocular fluid (IOF) and CTGF in IOP was performed by enzyme-linked immunosorbent assay (Invitrogen Thermo Fisher Sci., USA). Alleles rs1800470 (T869C) were determined by polymerase chain reaction (TaqMan Mutation Detection Assays Life-Technology test system, USA). For statistical studies, the MedStat and MedCalc v.15.1 software packages (MedCalc Software bvba) were used.

Results: Rs1800470 A/Acarriers had worse visual acuity (p=0.016) and higher central retinal thickness and volume (p<0.001) compared to G/G carriers. In DR the content of TGF-β1 in the blood and IOF and CTGF in IOF significantly exceeded that in controls (by 1.5-5.2 times; p<0.05). The highest content of both factors in DR compared to controls was determined in G/Aand A/Ars1800470 carriers. By stages of DR, a significant increase in the content of TGF-β1 in the blood and IOF and CTGF in IOF was established with maximum values in PDR. A higher content of both factors was established in G/Aand A/Acarriers compared to G/Gcarriers. In PDR, the blood content of TGF-β1 in A/A carriers was 1.2 times higher (p<0.05) than in G/Gcarriers. The increase in CTGF content in the IOF when comparing NPDR and PPDR was characteristic only for A/A carriers compared to G/Aand G/Gcarriers (1.2-1.5 times; p<0.05). In PDR, the content of this factor was equally high in G/Aand A/Acarriers compared to G/Grs1800470 carriers (1.3 times; p<0.05).

Conclusions: Thus, the content of both TGF-β1 and CTGF was higher in carriers of the G/Aand A/Agenotypes compared with the ancestral G/Ggenotype. Therefore, the clinically worse course of DR in carriers of the SNP rs1800470 of the TGFB1gene could be associated with a higher concentration of TGF-β1 and CTGF in the IOF of such patients.

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