The incidence rate over 10 years of naturally occurring, cancer related mutations in the basal core promoter of hepatitis B virus.
The incidence rate over 10 years of naturally occurring, cancer related mutations in the basal core promoter of hepatitis B virus.
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DOI：
10.1016/j.meegid.2015.07.020
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发表时间：
2015-08
期刊：
影响因子：
--
通讯作者：
Fang ZL
中科院分区：
文献类型：
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作者：
Wang XY;Harrison TJ;Chen QY;Li H;Li GJ;Liu MH;Hu LP;Tan C;Yang QL;Fang ZL
基础核心启动子（BCP）双突变的年发生率为3.8%。发病率随年龄增长呈下降趋势，高峰出现在生命早期。核苷酸（nt） 1762是第一个突变的有利位点。在nt 1762或1764有单一突变的病毒更容易发生双重突变。横断面分析显示，乙型肝炎病毒（HBV）基底核心启动子（BCP）双突变（nt 1762T, 1764A）的患病率随着年龄的增长而逐渐增加。我们的目标是确定10年内突变的发生率。研究对象从2004年建立的龙安队列中选择，其中59例HBV在BCP中具有nt 1762或1764单突变，342例基线时具有野生型BCP序列。分别在第3次和第10次年度访视时获得血清样本进行分析。结果显示，BCP双突变的年发生率为3.8%(95%可信区间[CI]: 1.4 ~ 6.2)，且随年龄增长呈下降趋势。发病率高峰在30-34岁年龄组。HBeAg阳性人群的发病率（5.5%）显著高于非HBeAg组（3.4%）（P < 0.05）。基因型C的发病率（4.8%）明显高于基因型B（2.8%）或基因型I（3.1%）。1762或1764位点突变的发生率（6.8%）显著高于野生型序列突变的发生率（3.8%）（P < 0.005）。nt 1762（0.7%）和nt 1764（0.03%）的单突变发生率差异有统计学意义（P < 0.05）。综上所述，BCP双突变发生率在35岁以后随年龄的增长呈下降趋势。在nt 1762或1764有单一突变的病毒更容易发生双重突变。Nt 1762是第一次突变的更常见位点。
The annual incidence rate of the basal core promoter (BCP) double mutations is 3.8%. The incidence rate tends to decrease with age and the peak appeared early in the life. Nucleotide (nt) 1762 is the favoured site of the first mutation. Viruses with a single mutation at nt 1762 or 1764 are more prone to develop double mutations. Cross-sectional analyses showed that the prevalence of basal core promoter (BCP) double mutations (nt 1762T, 1764A) of hepatitis B virus (HBV) gradually increases with age. We aimed to determine the incidence rate of the mutations over 10 years. Study subjects were selected from the Long An cohort established in 2004, including 59 with HBV with single mutations at nt 1762 or 1764 in the BCP and 342 with wild type BCP sequences at baseline. Their serum samples for analysis were obtained at the 3rd and 10th annual visits, respectively. The results showed that the annual incidence rate of BCP double mutations is 3.8% (95% confidence interval [CI]: 1.4–6.2) and tends to decrease with age. The peak incidence is in the 30–34 years age-group. The incidence rate in HBeAg positive individuals (5.5%) is significantly higher than in those without HBeAg (3.4%) (P < 0.05). The incidence rate is significantly higher in genotype C (4.8%) than in genotype B (2.8%) or I (3.1%). The incidence rate of the mutations (6.8%) developing from a single mutation at nt 1762 or 1764 is significantly higher than that (3.8%) from the wild type sequence (P < 0.005). The difference in incidence of single mutations between nt 1762 (0.7%) and 1764 (0.03%) is significant (P < 0.05). In conclusion, the incidence rate of BCP double mutations tends to decrease with age after the age of 35 years. Viruses with a single mutation at nt 1762 or 1764 are more prone to develop double mutations. Nt 1762 is the more common site of the first mutation.