TLR4 polymorphisms seem not to be associated with prediabetes and type 2 diabetes but predispose to diabetic retinopathy; TLR4 polymorphisms in glucose continuum

Abstract

Objectives. Compared to type 1 diabetes, the role of the immune and autoimmune pathogenetic mechanisms is much less studied in the type 2 diabetes. Toll-like receptors 4 (TLR4) have a leading role in inflammation, insulin resistance, and vascular damage. This study aimed to analyze the relationship between the polymorphisms in TLR4 gene and different stages in the glucose continuum from prediabetes to the type 2 diabetes and chronic microvascular complications.

Materials and Methods. The study included 113 patients with the type 2 diabetes, 29 participants with prediabetes, and 28 controls. Polymerase chain reaction (PCR) was used for genotyping Asp299Gly and Thr399Ile polymorphism, followed by restriction analysis.

Results. The difference in the genotype frequency for both polymorphisms in patients with the type 2 diabetes or prediabetes compared to that in controls was not significant. Patients with heterozygous genotype of Asp299Gly polymorphism had a higher prevalence of diabetic retinopathy (42.9%) than participants with homozygous genotype (9.0%) (OR [95%CI]=7.61 [1.41–41.08]; p=0.018). No association was established for diabetic polyneuropathy and nephropathy. Prevalence of chronic diabetes complications was not related to Thr399Ile polymorphism.

Conclusion. Our study demonstrates that Asp299Gly and Thr399Ile polymorphisms seem not to be associated with the type 2 diabetes and prediabetes but Asp299Gly may contribute to diabetic retinopathy predisposition.