TLR4 GENE POLYMORPHISM rs2149356 IN TYPE 2 DIABETES - POSSIBLE RELATIONSHIP WITH DIABETIC MACULAR EDEMA

Abstract

Background. Polymorphisms in the non-coding regions of the TLR4 gene are known to be associated with the risk of ocular complications of type 2 diabetes (T2DM), with some polymorphisms having no association, others increasing the risk, and some reducing the risk of complications. Aim: to establish the association of the TLR4 gene polymorphism rs2149356 with diabetic retinopathy (DR) and diabetic macular edema (DME) in T2DM. Materials and methods. The study included 81 patients (81 eyes) with T2DM, in whom, according to the guidelines of the American Academy of Ophthalmology (2002), DR and DME were detected, the control group consisted of 50 patients (50 eyes) with T2DM, normalized carbohydrate metabolism, DR 0 (no retinopathy) and absent DME. Genotypes of rs2149356 were determined by real-time polymerase chain reaction using the Gene Amp® PCR System 7500 amplifier (Applied Biosystems, USA) and TaqMan Mutation Detection Assays Life-Technology (USA). MedStat and MedCalc v.15.1 software packages (MedCalc Software bvba) were used for statistical research. Results. In this study, no association of the genetic polymorphism rs2149356 of the TLR4 gene with the development of DR and DME in T2DM was found (p=0.326). Stratification by stages of DR showed no dependence of the distribution of genotypes, while according to the degree of DME, the distribution of genotypes was definitely different in DME 3. Thus, among the carriers of the ancestral genotype G/G, none of DME 3 was found, the borderline level of the total retinal volume (TRV) was 6.7 mm3, above which DME 1 or DME 2 was determined. All carriers of the heterozygote G/T had DME 3, and for carriers of the minor homozygote T/T, two threshold values of TRV were determined: above 6.7 mm3, DME 1 or DME 2 was determined, and higher than 8.7 mm3 – DME 3. Analysis of the relationship between the rs2149356 TLR4 and the phenotype of patients showed greater central retinal thickness and TRV in heterozygous and minor homozygous T/T carriers, which corresponded to greater retinal damage compared to ancestral homozygous G/G carriers (p<0.001). Conclusion. Data were obtained on the association of diabetic retinal damage with the rs2149356 TLR4 – retinal edema was more pronounced in carriers of the T allele.