Hepatitis B virus subgenotypes and basal core promoter mutations in Indonesia.
OBJECTIVE
To identify the distribution of hepatitis B virus (HBV) subgenotype and basal core promoter (BCP) mutations among patients with HBV-associated liver disease in Indonesia.


METHODS
Patients with chronic hepatitis (CH, n = 61), liver cirrhosis (LC, n = 62), and hepatocellular carcinoma (HCC, n = 48) were included in this study. HBV subgenotype was identified based on S or preS gene sequence, and mutations in the HBx gene including the overlapping BCP region were examined by direct sequencing.


RESULTS
HBV genotype B (subgenotypes B2, B3, B4, B5 and B7) the major genotype in the samples, accounted for 75.4%, 71.0% and 75.0% of CH, LC and HCC patients, respectively, while the genotype C (subgenotypes C1, C2 and C3) was detected in 24.6%, 29.0%, and 25.0% of CH, LC, and HCC patients, respectively. Subgenotypes B3 (84.9%) and C1 (82.2%) were the main subgenotype in HBV genotype B and C, respectively. Serotype adw2 (84.9%) and adrq+ (89.4%) were the most prevalent in HBV genotype B and C, respectively. Double mutation (A1762T/G1764A) in the BCP was significantly higher in LC (59.7%) and HCC (54.2%) than in CH (19.7%), suggesting that this mutation was associated with severity of liver disease. The T1753V was also higher in LC (46.8%), but lower in HCC (22.9%) and CH (18.0%), suggesting that this mutation may be an indicator of cirrhosis.


CONCLUSIONS
HBV genotype B/B3 and C/C1 are the major genotypes in Indonesia. Mutations in BCP, such as A1762T/G1764A and T1753V, might have an association with manifestations of liver disease.
Utama
Andi
A
Molecular Epidemiology Division, Mochtar Riady Institute for Nanotechnology, Jalan Boulevard Jend, Sudirman 1688, Lippo Karawaci, Tangerang, Banten 15810, Indonesia. autama@mrinstitute.org
Purwantomo
Sigit
S
Siburian
Marlinang Diarta
MD
Dhenni
Rama
R
Gani
Rino Alvani
RA
Hasan
Irsan
I
Sanityoso
Andri
A
Miskad
Upik Anderiani
UA
Akil
Fardah
F
Yusuf
Irawan
I
Achwan
Wenny Astuti
WA
Soemohardjo
Soewignjo
S
Lelosutan
Syafruddin A R
SA
Martamala
Ruswhandi
R
Lukito
Benyamin
B
Budihusodo
Unggul
U
Lesmana
Laurentius Adrianus
LA
Sulaiman
Ali
A
Tai
Susan
S
D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000821:virology; D005260:Female; D005814:Genes, Viral; D005838:Genotype; D006509:Hepatitis B / Q000453:epidemiology / Q000821:virology*; D006512:Hepatitis B Core Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D007214:Indonesia; D008103:Liver Cirrhosis / Q000821:virology; D008113:Liver Neoplasms / Q000821:virology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA
D006512:Hepatitis B Core Antigens
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