A thymine-adenine dinucleotide repeat polymorphism near IL28B is associated with spontaneous clearance of hepatitis C virus.
BACKGROUND
Genome-wide association studies have revealed several single-nucleotide polymorphisms around interleukin 28B (IL28B) that are strongly associated with hepatitis C virus (HCV) clearance. However, their predictive value is not perfect, which suggests that other genetic factors may also be involved in HCV clearance. We previously reported a wide variation in the length of a thymine-adenine (TA) dinucleotide repeat in the promoter region of IL28B and that the transcriptional activity of the promoter increased gradually in a TA repeat length-dependent manner.


METHODS
We determined the length of the TA repeats of 1,060 Japanese and 201 African-American samples to investigate the relation to spontaneous HCV clearance.


RESULTS
The distribution of the TA repeats greatly differed between the two ethnicities. The variation ranged from 10 to 18 repeats, and the most frequent allele, 12, accounted for over 80% for Japanese. The African-American data showed a gently sloping distribution, and the allele with six repeats was detected only in the African-American sample. The TA repeats 11 or greater were correlated with spontaneous clearance. Multiple logistic regression analysis extracted the genotype of the TA repeats as an independent factor in both the Japanese [p = 0.0004, odds ratio (OR) = 13.02 95% confidence interval (CI) = 2.59-237.0] and African-American (p = 0.027, OR = 3.70 95% CI = 1.16-11.8) populations.


CONCLUSIONS
A long TA repeat in the promoter region of IL28B was associated with spontaneous HCV clearance. Although its efficacy may be limited in Japanese population because of its allele distribution, this novel genetic factor will be useful for predicting HCV clearance especially for the African Americans.
Department of Hepatic Diseases, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1 Kohonodi, Ichikawa, 272-8516, Chiba, Japan.|General Internal Medicine Department, Kyushu University Hospital, Fukuoka, 812-8582, Japan.
Satoshi
S
Hiramine
Department of Hepatic Diseases, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1 Kohonodi, Ichikawa, 272-8516, Chiba, Japan.
Masaya
M
Sugiyama
General Internal Medicine Department, Kyushu University Hospital, Fukuoka, 812-8582, Japan.
Norihiro
N
Furusyo
Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, 890-8544, Japan.
Hirofumi
H
Uto
Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, 890-8544, Japan.
Akio
A
Ido
Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, 890-8544, Japan.
Hirohito
H
Tsubouchi
Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, 990-9585, Japan.
Hisayoshi
H
Watanabe
Department of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, 990-9585, Japan.
Yoshiyuki
Y
Ueno
Department of Hepatic Diseases, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1 Kohonodi, Ichikawa, 272-8516, Chiba, Japan.
Masaaki
M
Korenaga
Department of Hepatic Diseases, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1 Kohonodi, Ichikawa, 272-8516, Chiba, Japan.
Kazumoto
K
Murata
Department of Hepatic Diseases, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1 Kohonodi, Ichikawa, 272-8516, Chiba, Japan.
Naohiko
N
Masaki
General Internal Medicine Department, Kyushu University Hospital, Fukuoka, 812-8582, Japan.
Jun
J
Hayashi
Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA.
David L
DL
Thomas
Department of Hepatic Diseases, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1 Kohonodi, Ichikawa, 272-8516, Chiba, Japan. mmizokami@hospk.ncgm.go.jp.
Masashi
M
Mizokami
D000225:Adenine / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D004279:DNA, Viral / Q000235:genetics*; D018900:Dinucleotide Repeats; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D013941:Thymine / Q000378:metabolism*; D055815:Young Adult; D000095022:Interferon Lambda
D000225:Adenine; D004279:DNA, Viral; D007372:Interferons; D007378:Interleukins; D013941:Thymine; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
Genetic marker; Interferon lambda 3; Microsatellite