Transcription Factor Binding Site Polymorphisms within DIO2 and GADD45A genes increase the risk of liver disease progression in chronic hepatitis b carriers

The aim of this study was to determine the association of single nucleotide polymorphisms (SNPs) within transcription factor binding sites with the progression of liver damage in chronic hepatitis B patients. The study group consisted of 284 chronic hepatitis B (CHB) patients, including individuals with mild fibrosis (32.5%), moderate to severe fibrosis (27.5%), liver cirrhosis – LC (22%), hepatocellular carcinoma – HCC (5%), and no fibrosis (13%) participants. SNP genotyping was performed by mass spectrometry, and included SNPs: DIO2 (rs225017, rs225014), PPARG (rs10865710, rs2016520), ATF3 (rs11119982), AKT3 (rs12031994), and GADD45A (rs532446, rs37834688), TBX21 (rs4794067). The patients’ susceptibility to advanced liver fibrosis was independly associated with rs225014 TT (DIO2) and rs10865710 CC (PPARG), whereas cirrhosis occurrence was more common in individuals with GADD45A rs532446 TT, and ATF3 rs11119982 TT genotypes. Moreover, DIO2 rs225014 CC variant was more common patients with diagnosed hepatocellular carcinoma (HCC). These results suggest the potential role of above SNPs in HBV-induced liver damage in a Caucasian population.