Detection of YMDD motif mutants by oligonucleotide chips in lamivudine-untreated patients with chronic hepatitis B virus infection.
Lamivudine, a nucleoside analogue, has been used widely as an effective antiviral agent for the treatment of patients with chronic hepatitis B virus (HBV) infection. However, the YMDD motif mutation of HBV polymerase resistant to lamivudine occurs very frequently after long term therapy. We developed an oligonucleotide chip for the detection of YMDD motif mutants resistant to lamivudine and investigated the prevalence of the mutants in patients with chronic HBV infection who had not been treated by lamivudine before. Forty patients who had not been treated with lamivudine were included in this study. Serum samples were tested by the oligonucleotide chips designed for detection of wild-type YMDD motif, M552V and M552I. Samples were confirmed by restriction fragment length polymorphism (RFLP) and direct sequencing. M552I mutants were detected by the oligonucleotide chips in 7.5% (3/40) of chronic HBV infected patients (2 chronic hepatitis and 1 cirrhosis). The results were in accordance with those of RFLP. YMDD motif mutants occur as natural genome variabilities in patients with chronic HBV infection who had not been treated with lamivudine before. Oligonucleotide chip technology is a reliable and useful diagnostic tool for the detection of mutants resistant to antiviral therapy in chronic HBV infection.
Heo
Jeong
J
Department of Internal Medicine, Pusan National University College of Medicine, Busan, Korea.
Cho
Mong
M
Kim
Hyung Hoi
HH
Shin
Young Min
YM
Jang
Hyun Jung
HJ
Park
Hee Kyung
HK
Kim
Cheol Min
CM
Kim
Gwang Ha
GH
Kang
Dae Hwan
DH
Song
Geun Am
GA
Yang
Ung Suk
US
D000293:Adolescent; D000328:Adult; D020816:Amino Acid Motifs; D002908:Chronic Disease; D005260:Female; D014644:Genetic Variation; D006509:Hepatitis B / Q000188:drug therapy*; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D012150:Polymorphism, Restriction Fragment Length; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA
D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine