泰国人群中胸腺嘧啶 - 腺嘌呤二核苷酸重复序列、IL28B和IFNL4的患病率及其与丙型肝炎感染自发清除和治疗结果的相关性
Prevalence of Thymine--Adenine Dinucleotide Repeat, IL28B and IFNL4 in Thai Population and Correlation with Spontaneous Clearance and Treatment Outcome of Hepatitis C Infection.
作者信息
Thong Vo Duy, Wasitthankasem Rujipat, Tangkijvanich Pisit, Vongpunsawad Sompong, Poovorawan Yong
机构信息
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.
Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
出版信息
PLoS One. 2015 May 4;10(5):e0125400. doi: 10.1371/journal.pone.0125400. eCollection 2015.
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.
背景
白介素 - 28B（IL28B）基因多态性是丙型肝炎病毒（HCV）治疗中持续病毒学应答（SVR）的有力基线预测指标。IL28B调控区中胸腺嘧啶 - 腺嘌呤二核苷酸重复序列（TA）n的长度可影响干扰素转录。为确定其在HCV感染中的预测价值，我们探讨了包括（TA）n基因型、临床特征、干扰素 - λ - 3（IFNL3）和干扰素 - λ - 4（IFNL4）多态性以及HCV治疗结果等因素之间的相关性。
方法
分析了492例慢性HCV感染患者、101例自发清除HCV的个体以及123名健康献血者（对照组）的血清。通过直接测序对（TA）n进行基因分型。使用巢式PCR和测序鉴定rs12979860（IFNL3），通过实时PCR鉴定ss469415590（IFNL4）。
结果
自发清除HCV的个体与慢性HCV感染个体之间（TA）n的分布相似，但与健康对照组有显著差异。与至少有一个（TA）n <12等位基因的个体相比，两个（TA）n等位基因≥12的个体SVR率显著更高。在感染HCV - 1、HCV - 3和HCV - 6的患者中均观察到这种强相关性。（TA）n基因型与HCV病毒载量、ALT水平和肝脏硬度无关，但与血小板计数相关（p<0.001）。相比之下，rs12979860（CC）和ss469415590（TT/TT）基因型仅在HCV - 1患者中与更高的SVR率相关。
结论
（TA）n基因型与HCV感染的自发清除无关，但与感染HCV - 1、HCV - 3和HCV - 6的患者的治疗反应相关。相比之下，IFNL3和IFNL4多态性仅对感染HCV - 1的患者的治疗结果具有预测性。
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