A thymine–adenine dinucleotide repeat polymorphism near IL28B is associated with spontaneous clearance of hepatitis C virus

Satoshi Hiramine, Masaya Sugiyama, Norihiro Furusyo, Hirofumi Uto, Akio Ido, Hirohito Tsubouchi, Hisayoshi Watanabe, Yoshiyuki Ueno, Masaaki Korenaga, Kazumoto Murata, Naohiko Masaki, Jun Hayashi, David L. Thomas, Masashi Mizokami

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)1069-1077
Number of pages9
JournalJournal of gastroenterology
Volume50
Issue number10
DOIs
Publication statusPublished - Oct 1 2015

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Dinucleotide Repeats
Interleukins
Hepacivirus
African Americans
Alleles
Genetic Promoter Regions
Odds Ratio
Confidence Intervals
Genome-Wide Association Study
Population
Single Nucleotide Polymorphism
Logistic Models
Genotype
Regression Analysis

All Science Journal Classification (ASJC) codes

  • Gastroenterology

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A thymine–adenine dinucleotide repeat polymorphism near IL28B is associated with spontaneous clearance of hepatitis C virus. / Hiramine, Satoshi; Sugiyama, Masaya; Furusyo, Norihiro; Uto, Hirofumi; Ido, Akio; Tsubouchi, Hirohito; Watanabe, Hisayoshi; Ueno, Yoshiyuki; Korenaga, Masaaki; Murata, Kazumoto; Masaki, Naohiko; Hayashi, Jun; Thomas, David L.; Mizokami, Masashi.

In: Journal of gastroenterology, Vol. 50, No. 10, 01.10.2015, p. 1069-1077.

Research output: Contribution to journalArticle

Hiramine, S, Sugiyama, M, Furusyo, N, Uto, H, Ido, A, Tsubouchi, H, Watanabe, H, Ueno, Y, Korenaga, M, Murata, K, Masaki, N, Hayashi, J, Thomas, DL & Mizokami, M 2015, 'A thymine–adenine dinucleotide repeat polymorphism near IL28B is associated with spontaneous clearance of hepatitis C virus', Journal of gastroenterology, vol. 50, no. 10, pp. 1069-1077. https://doi.org/10.1007/s00535-015-1056-1
Hiramine, Satoshi ; Sugiyama, Masaya ; Furusyo, Norihiro ; Uto, Hirofumi ; Ido, Akio ; Tsubouchi, Hirohito ; Watanabe, Hisayoshi ; Ueno, Yoshiyuki ; Korenaga, Masaaki ; Murata, Kazumoto ; Masaki, Naohiko ; Hayashi, Jun ; Thomas, David L. ; Mizokami, Masashi. / A thymine–adenine dinucleotide repeat polymorphism near IL28B is associated with spontaneous clearance of hepatitis C virus. In: Journal of gastroenterology. 2015 ; Vol. 50, No. 10. pp. 1069-1077.
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abstract = "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.",
author = "Satoshi Hiramine and Masaya Sugiyama and Norihiro Furusyo and Hirofumi Uto and Akio Ido and Hirohito Tsubouchi and Hisayoshi Watanabe and Yoshiyuki Ueno and Masaaki Korenaga and Kazumoto Murata and Naohiko Masaki and Jun Hayashi and Thomas, {David L.} and Masashi Mizokami",
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T1 - A thymine–adenine dinucleotide repeat polymorphism near IL28B is associated with spontaneous clearance of hepatitis C virus

AU - Hiramine, Satoshi

AU - Sugiyama, Masaya

AU - Furusyo, Norihiro

AU - Uto, Hirofumi

AU - Ido, Akio

AU - Tsubouchi, Hirohito

AU - Watanabe, Hisayoshi

AU - Ueno, Yoshiyuki

AU - Korenaga, Masaaki

AU - Murata, Kazumoto

AU - Masaki, Naohiko

AU - Hayashi, Jun

AU - Thomas, David L.

AU - Mizokami, Masashi

PY - 2015/10/1

Y1 - 2015/10/1

N2 - 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.

AB - 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.

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