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Investigation of rs11536889 + 3725G/C polymorphism of the TLR4 gene in patients with autoimmune and chronic viral hepatitis C

Kucherenko A.M., rz L.V., Bvz .I., Bulavenko V.I., Antypkin Y.G., Berezenko V.S., Dyba M.B., Pampukha V.M., Gorodna O.V., Livshits L..

 




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: 2,7045,66). Thus, TLR4 rs11536889 C allele is associated with higher level of fibrotic liver damage in patients with chronic hepatitis.

Key words: Autoimmune hepatitis, Viral hepatitis C, Liver fibrosis, Single nucleotide polymorphism, Toll-like receptor TLR4

Tsitologiya i Genetika 2019, vol. 53, no. 4, pp. 41-49

E-mail: livshits imbg.org.ua

Kucherenko A.M., rz L.V., Bvz .I., Bulavenko V.I., Antypkin Y.G., Berezenko V.S., Dyba M.B., Pampukha V.M., Gorodna O.V., Livshits L.. Investigation of rs11536889 + 3725G/C polymorphism of the TLR4 gene in patients with autoimmune and chronic viral hepatitis C, Tsitol Genet., 2019, vol. 53, no. 4, pp. 41-49.

In "Cytology and Genetics":
A. M. Kucherenko, L. V. Moroz, T. I. Bevz, V. I. Bulavenko, Y. G. Antypkin, V. S. Berezenko, M. B. Dyba, V. M. Pampukha, O. V. Gorodna, L. A. Livshits Investigation of rs11536889 + 3725G/C Polymorphism of the TLR4 Gene in Patients with Autoimmune and Chronic Viral Hepatitis C, Cytol Genet., 2019, vol. 53, no. 4, pp. 300306
DOI: 10.3103/S0095452719040078


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