Enhanced Gene Expression of Toll-Like Receptors 3, 7, and 9 in Thalassemia Patients: Implications for Inflammation and Potential Therapeutic Targets

Abstract

Thalassemia is an inherited blood disorder marked by reduced hemoglobin synthesis, which leads to chronic anemia and systemic complications, among them immune dysregulation and chronic inflammation. The current study aims at investigating the gene expression of TLR3, 7, and 9 in thalassemia patients and their relation to the inflammatory markers. Because we used a larger, diverse sample population and a longitudinal study design, we were able to reveal significant upregulation of TLR3 and TLR9 in thalassemia patients compared to healthy controls strongly correlated with the high levels of various proinflammatory cytokines. We have further demonstrated that different genetic polymorphisms in the promoter regions of TLR3 and TLR9 alters the binding of transcription factors and thus can be possible causes of the dysregulation of these genes. Our results implicate that TLR3 and TLR9 themselves play a very important role in the inflammatory response in thalassemia and are therefore potential therapeutic targets for mitigating inflammation to improve outcomes in these patients.