engleski

Single nucleotide polymorphisms of CXCL9 (rs10336) and CXCL10(rs3921) are not associated with hepatocellular carcinoma in alcoholic liver disease

Background: Multiple risk factors interacting with the genetic background increase the risk of hepatocellular carcinoma (HCC) in chronic liver diseases. C-X-C chemokines have been implicated in different mechanisms of hepatocarcinogenesis. Recent data showed an association between single nuclear polymorphism (SNP) for CXCL9 and 10 genes and the development of liver fibrosis. The aim of this study was to examine the association of CXCL9 and CXCL10 SNPs and HCC. Methods: DNA was isolated from the blood of 158 patients transplanted due to alcoholic liver disease (52 HCC and 106 age-and sex-matched non- HCC patients) between 1/2009- 3/2017 in UH Merkur, Zagreb, Croatia. Polymorphisms of CXCL9 (rs10336) and CXCL10 (rs3921) were determined by PCR using commercially available TaqMan SNP assays. HCC diagnosis and staging according to Milan criteria was established on the explanted livers. Results: Genotypes were in Hardy-Weinberg equilibrium (p>0.05), with strong linkage disequilibrium (D‘=0.999, r=0.986) between CXCL9 and CXCL10. In the HCC group 22 (42.3%) patients had GG, 21 (40.4%) had AG and 9 (17.3%) had AA genotype of the CXCL9 polymorphism, with similar genotype distribution observed in the non-HCC group, where 37 (34.9%) patients had GG, 52 (49.1%) had AG and 17 (16%) had AA genotype. We found no association between CXCL9 genotypes and HCC in codominant, dominant, recessive, overdominant or log-additive model (p>0.05). Similar results were obtained for CXCL10 genotypes. Interestingly, we observed a small increase in the proportion of patients with HCC beyond Milan criteria across genotypes of CXCL9 (AA/AG/GG ; 22.2%/28.6%/36.4%, respectively) and CXCL 10, but without reaching statistical significance. Conclusion: Our data suggest that single nucleotide polymorphisms of CXCL9 (rs10336) and CXCL10 (rs3921) are not associated with alcohol- related HCC. However, further research is needed to determine their association with the morphological criteria and their possible role in hepatocarcinogenesis.

single nucleotide polymorphisms ; hepatocellular carcinoma ; alcoholic liver disease

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