IL28B 基因多态性与丙型肝炎病毒感染自发清除患者的美国肝脏脂肪变化。
IL28B gene polymorphisms and US liver fatty changes in patients who spontaneously cleared hepatitis C virus infection.
机构信息
Clinica Malattie Infettive e Tropicali, Department of Clinical Medicine, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy.
出版信息
PLoS One. 2013 Aug 1;8(8):e67301. doi: 10.1371/journal.pone.0067301. Print 2013.
BACKGROUND
Recent clinical studies have shown that the presence of CC genotype in the rs12979860 region of IL28B gene is associated with an increase in the probability of spontaneous clearance of hepatitis C virus (HCV). Moreover, IL28B polymorphism seems to influence the probability of developing liver steatosis in chronic HCV patients.
AIMS
The aims of our clinical study were 1) to verify the distribution of IL28B genotypes (CC, CT or TT) among subjects with spontaneous clearance of HCV infection and 2) to examine the correlation between IL28B polymorphism and hepatic steatosis among these subjects.
METHODS AND PATIENTS
We enrolled 41 subjects with spontaneous resolution of HCV infection (detectable serum anti-HCV but undetectable HCV-RNA) and 134 healthy controls from the same geographical area. The IL28B single-nucleotide polymorphism (SNP) rs12979860 was genotyped by using a Pyrosequencing™ technique. The presence of steatosis was assessed by liver biopsy or ultrasound examination in the 41 study subjects.
RESULTS
CC, CT and TT-genotypes of the SNP rs1979860 were found in 66%, 24% and 10% of the subjects who spontaneously cleared HCV and in 31%, 54% and 15% of controls, respectively (p = 0.0003). Among the study subjects, females with CC-genotype were significantly more represented (p = 0.02). Hepatic steatosis did not correlate with IL28B genotype (p = 0,14) but only with a high body mass index (BMI) value (p = 0.03).
CONCLUSIONS
Female subjects carrying IL28B CC-genotype are significantly more represented among Italian patients who spontaneously cleared HCV infection. In addition, among these subjects, the presence of liver steatosis does not correlate with IL28B genotype but is solely related to the occurrence of high BMI. Thus, the association between IL28B polymorphism and steatosis in chronic HCV patients requires the presence of active HCV replication to occur, while in subjects who have cleared the infection, the mechanism(s) inducing liver steatosis are independent from IL28B profile.
背景
最近的临床研究表明，白细胞介素 28B（IL28B）基因 rs12979860 区域的 CC 基因型的存在与丙型肝炎病毒（HCV）自发清除的概率增加有关。此外，IL28B 多态性似乎影响慢性 HCV 患者发生肝脂肪变性的概率。
目的
本临床研究的目的是 1）验证 IL28B 基因型（CC、CT 或 TT）在 HCV 感染自发清除患者中的分布情况，2）检测这些患者中 IL28B 多态性与肝脂肪变性之间的相关性。
方法和患者
我们招募了 41 名 HCV 感染自发清除患者（可检测到血清抗 HCV，但不可检测到 HCV-RNA）和来自同一地理区域的 134 名健康对照者。采用焦磷酸测序技术对 IL28B 单核苷酸多态性（SNP）rs12979860 进行基因分型。在 41 名研究对象中，通过肝活检或超声检查评估脂肪变性的存在。
结果
在 HCV 自发清除的患者中，SNP rs1979860 的 CC、CT 和 TT 基因型分别占 66%、24%和 10%，而在对照组中，分别占 31%、54%和 15%（p=0.0003）。在研究对象中，携带 CC 基因型的女性明显更多（p=0.02）。肝脂肪变性与 IL28B 基因型无相关性（p=0.14），仅与高体重指数（BMI）值相关（p=0.03）。
结论
在意大利 HCV 感染自发清除的患者中，携带 IL28B CC 基因型的女性明显更多。此外，在这些患者中，肝脂肪变性的存在与 IL28B 基因型无关，而仅与 BMI 升高有关。因此，IL28B 多态性与慢性 HCV 患者的脂肪变性之间的关联需要 HCV 复制的存在才能发生，而在清除感染的患者中，诱导肝脂肪变性的机制与 IL28B 谱无关。
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