A thymine-adenine dinucleotide repeat polymorphism near IL28B is associated with spontaneous clearance of hepatitis C virus.
A thymine-adenine dinucleotide repeat polymorphism near IL28B is associated with spontaneous clearance of hepatitis C virus.
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DOI：
10.1007/s00535-015-1056-1
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发表时间：
2015-10
影响因子：
6.3
通讯作者：
Mizokami M
中科院分区：
文献类型：
--
作者：
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
全基因组关联研究揭示了白介素28B(IL28B)周围的几个单核苷酸多态与丙型肝炎病毒(HCV)的清除密切相关。然而，它们的预测价值并不完美，这表明其他遗传因素也可能参与了丙型肝炎病毒的清除。我们先前报道了IL28B启动子区域胸腺嘧啶(TA)二核苷酸重复序列长度的广泛变异，并且启动子的转录活性以TA重复序列长度依赖的方式逐渐增加。我们测定了1,060名日本人和201名非洲裔美国人样本的TA重复序列长度，以研究其与自发清除丙型肝炎病毒的关系。TA重复序列在两个种族中的分布有很大差异。变异范围为10~18个重复，其中最常见的等位基因12，占日本人的80%以上。非洲裔美国人的数据显示出一种缓坡分布，只有在非洲裔美国人样本中才检测到有六个重复的等位基因。TA重复数大于或等于11个与自发清除相关。多因素Logistic回归分析显示，TA重复序列的基因型在日本人[P=0.0004，OR=13.02，95%可信区间(CI)=2.59-237.0]和非裔美国人(P=0.027，OR=3.70，95%CI=1.16-11.8)中都是一个独立的影响因素。IL28B启动子区域的长TA重复序列与自发的丙型肝炎病毒清除有关。尽管由于其等位基因分布，其在日本人群中的疗效可能有限，但这一新的遗传因素将有助于预测丙型肝炎病毒的清除，特别是对非裔美国人。
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. 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. 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. 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.