Investigating the distributions of three common variants of TLR۹ and its mRNA expression levels in NAFL patients without and with liver fibrosis compared to healthy controls

Background and Aim: Recent studies stablished that, the plasma level of mitochondrial DNA, increases in NASH patients and animal models. Other studies have shown that, mitochondrial DNA can activate TLR۹ downstream signaling, in hepatocytes and triggers inflammatory and fibrotic pathways. Based on these findings, present study was developed to investigate the association of mRNA expression levels of TLR۹ gene and three common genetic polymorphisms of this gene in NAFL patients with different stages of hepatic fibrosis compared to healthy controls.Methods: Twenty-two healthy controls and ۷۰ NAFL patients with liver fibrosis were enrolled. Based on the fibroscan scores, patients divided into three groups: F۰-F۱, F۲-F۳ and F۴. Genotype frequency distribution of rs۳۵۲۱۴۰, rs۵۷۴۳۸۳۶ and rs۱۸۷۰۸۴ were determined using RFLP-PCR. The mRNA levels of TLR۹ also measured using real-time PCR.Results: Our results showed that, none of the studied genetic polymorphisms had a significant association with the risk of hepatic fibrosis development in NAFL patients (P=۰.۰۵). While the mRNA expression levels of TLR۹ was significantly higher in both patients with F۰-F۱ and F۲-F۳ fibrosis degree compared to healthy controls (P=۰.۰۳۲ and P=۰.۰۰۷ respectively).Conclusion: Overall, this study, for the first time, showed that overexpression of TLR۹ mRNA, independent to its genetic polymorphism, may increases the susceptibility of hepatic fibrosis development in NAFL patients.

Keywords:

Toll like receptor ۹ , inflammation , genetic polymorphism , hepatic fibrosis