SUMMARY. 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 accord-ing to Hardy-Weinberg equilibrium. AH and CHC patients were divided according to METAVIR fibrosis score two groups – with stage 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-fold 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.
Keywords: Autoimmune hepatitis, Viral hepatitis C, Liver fibrosis, Single nucleotide polymorphism, Toll-like receptor TLR4
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