Investigation of rs11536889 + 3725G/C Polymorphism of the TLR4 Gene in Patients with Autoimmune and Chronic Viral Hepatitis C

Abstract

Toll-like receptor 4 (encoded by TLR4 gene) has a variety of functions, including tissue homeostasis, regulation of cell death and survival via activation of signaling pathways which lead to interferon regulatory factor 3 (IRF-3) activation and type I interferon production. TLR4 may have a crucial role in pathogenesis of complex and infectious diseases. Functional polymorphism TLR4 +3725G/C substitution (rs11536889) leads to faster transcript degradation and receptors number decrease. The study investigated TLR4 rs11536889 genotype and allele distribution in healthy volunteers from Ukraine (n = 155), autoimmune hepatitis (AH) children (n = 56) and chronic hepatitis C (CHC) adult patients with various fibrosis severity stages (n = 78). Genotyping was performed by allele-specific PCR. The obtained genotype frequencies in Ukrainian population were: GG genotype—0.813, GC—0.168, CC—0.019 and showed no significant deviation from the ones expected according to Hardy-Weinberg equilibrium. AH and CHC patients were divided according to METAVIR fibrosis score into two groups—with stages F1–F2, and with F3–F4. The frequency of rs11536889 C allele carriers were higher in the group of AH patients with F3–F4 (0.179) comparing to patients with F1–F2 (0.071). This data did not reach the threshold for significance but showed a trend toward association between C allele carriers and higher fibrosis degree. Moreover, the significantly (p < 0.05) higher frequency of C allele carriers was observed in CHC patients with higher fibrosis degree (0.400) compared to patients with lower degree (0.057). Severe liver damage risk in such individuals is 11 increased (OR = 11.11, 95% CI: 2.70–45.66). Thus, TLR4 rs11536889 C allele is associated with higher level of fibrotic liver damage in patients with chronic hepatitis.