Mutations of glucocorticoid responsive element of HBV DNA.

The mutation of glucocorticoid responsive element (GRE) of HBV DNA obtained from a patient with chronic hepatitis B was evaluated. This patient showed fatal course by glucocorticoid administration. The HBV DNA from this patient (GRE-M) and two patients with HBeAg positive chronic hepatitis B (GRE-W1,2) whose HBV DNA have few mutations, were examined. The 212 bp region from nt.274 to nt.485 (GRE region) was amplified by PCR and the nucleotide sequence was determined. A base mismatched sequence of the latter half of the GRE consensus sequence was confirmed at nt.296-301 (G1), nt.347-352 (G2), nt.359-364 (G3), and nt.473-478 (G4). Also one base mismatched sequence of the AP-1 response element was detected at nt.331-337 (A1). The nucleotide substitutions in GRE-M generate three putative loop formation sites, four bases in length, from nt.22 to nt.31 (L1), nt.35 to nt.42 (L2), and nt.74 to nt.83 (L3). The L1 was located just upstream of the G1. The L2 was located between the A1 and the G2. These mutations followed by three-dimensional form change may affect the responses to glucocorticoid.