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 infl ammation, insulin resistance, and vascular damage. Th is study aimed to analyze the relationship between the polymorphisms in TLR4 gene and diff erent stages in the glucose continuum from prediabetes to the type 2 diabetes and chronic microvascular complications.Materials and Methods. Th e 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 Th r399Ile polymorphism, followed by restriction analysis.Results. Th e diff erence in the genotype frequency for both polymorphisms in patients with the type 2 diabetes or prediabetes compared to that in controls was not signifi cant. 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 Th r399Ile polymorphism.Conclusion. Our study demonstrates that Asp299Gly and Th r399Ile polymorphisms seem not to be associated with the type 2 diabetes and prediabetes but Asp299Gly may contribute to diabetic retinopathy predisposition.

Toll like receptor 4 gene Asp299Gly polymorphism increases the risk of diabetic microvascular complications: a meta analysis

“…Nevertheless, no significant association was observed between TLR4 Asp299Gly gene polymorphism and DN and diabetic neuropathy subgroup (p > 0.05). The studies of Buraczynska et al [ 16 ], Buraczynska et al [ 18 ], and Zaharieva [ 20 ] were consistent with our results, which further confirmed that TLR4 Asp299Gly gene polymorphism was significantly associated with increased risk of DR. Therefore, we can infer that although DR, DN and diabetic neuropathy were included in microvascular complications, there still exists some differences in the pathogenesis.…”

“…We reviewed the titles and abstracts, 773 articles were excluded. By reading the full text to exclude duplicate, non-English, non-Asp299Gly locus, original text cannot obtain genotype and allele frequency excluded 22, 7 articles were initially included [ 15 – 20 , 24 ]. Through data collation, 1 literature with no mutation in Asp299Gly site was not included in this meta analysis [ 24 ].…”

“…Through data collation, 1 literature with no mutation in Asp299Gly site was not included in this meta analysis [ 24 ]. Finally, 6 articles that met the inclusion criteria were included in this study [ 15 – 20 ], including 11 case–control studies. The main characteristics of the selected studies are listed in Table 1 , with a total of 11 studies of 1834 cases and 4069 controls for investigating the association between DMI and TLR4 Asp299Gly polymorphism.…”

miRNA‑766 induces apoptosis of human colon cancer cells through the p53/Bax signaling pathway by MDM4

“…miR-191, which locates in human 3p21.3, has been found to be overexpressed in numerous types of human tumor (18). For example, a high expression of miR-191 has been found in liver, stomach, large intestine, prostate, and breast cancer (19).…”

Curcumin Analogs Reduce Stress and Inflammation Indices in Experimental Models of Diabetes

“…We have previously shown that some curcumin analogs directly bind to a TLR4 co-receptor, myeloid differentiation protein 2 and inhibit TLR4 signaling (50,51). TLR4 is implicated in diabetic nephropathy (52,53), retinopathy (54), and cardiomyopathy (55). TLR4 inhibition also prevents HG-induced NF-κB activation and production of inflammatory cytokines (56).…”