Prevalence of Thymine--Adenine Dinucleotide Repeat, IL28B and IFNL4 in Thai Population and Correlation with Spontaneous Clearance and Treatment Outcome of Hepatitis C Infection.
BACKGROUND
The interleukin-28B (IL28B) gene polymorphism is a strong baseline predictor of sustained virological response (SVR) in hepatitis C virus (HCV) treatment. The length of thymine--adenine dinucleotide repeats, or (TA)n, in the regulatory region of IL28B can affect interferon transcription. In order to determine predictive values in HCV infection, we explored the correlation among factors including (TA)n genotypes, clinical features, interferon-λ-3 (IFNL3) and interferon-λ-4 (IFNL4) polymorphisms, and HCV treatment outcome.


METHODS
Sera from 492 patients with chronic HCV infection, 101 individuals with spontaneous HCV clearance and 123 healthy blood donors (control group) were analyzed. Genotyping of the (TA)n was performed by direct sequencing. The rs12979860 (IFNL3) was identified using nested PCR and sequencing, while ss469415590 (IFNL4) was identified by real-time PCR.


RESULTS
The distribution of (TA)n was similar between individuals with spontaneous HCV clearance and chronic HCV infection, but differed significantly from healthy controls. Individuals with both (TA)n alleles ≥ 12 had significantly higher SVR rate compared to individuals with at least one (TA)n <12 allele. This strong correlation was seen for patients infected with HCV-1, HCV-3, and HCV-6. The (TA)n genotypes were not associated with HCV viral load, ALT levels and liver stiffness, but were correlated with platelet counts (p<0.001). In contrast, rs12979860 (CC) and ss469415590 (TT/TT) genotypes were associated with higher SVR rated only in patients with HCV-1.


CONCLUSIONS
The (TA)n genotypes were not associated with spontaneous clearance of HCV infection but associated with treatment response in patients infected with HCV-1, HCV-3 and HCV-6. In contrast, IFNL3 and IFNL4 polymorphisms were predictive of treatment outcome only for patients infected with HCV-1.
Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Department of Internal Medicine, Division of Gastroenterology and Hepatology, Faculty of Medicine, University of Medicine and Pharmacy, Ho Chi Minh, Vietnam.
Vo Duy
VD
Thong
Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Rujipat
R
Wasitthankasem
Research Unit of Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Pisit
P
Tangkijvanich
Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Sompong
S
Vongpunsawad
Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Yong
Y
Poovorawan
D000225:Adenine; D000328:Adult; D000483:Alleles; D000998:Antiviral Agents / Q000627:therapeutic use; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D018900:Dinucleotide Repeats; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D006526:Hepatitis C / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000235:genetics / Q000821:virology; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D013785:Thailand; D013941:Thymine; D016896:Treatment Outcome; D019562:Viral Load; D000095022:Interferon Lambda
D000225:Adenine; D000998:Antiviral Agents; D007372:Interferons; D007378:Interleukins; D013941:Thymine; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C579163:IFNL4 protein, human