Truelove Ann L, Oleksyk Taras K, Shrestha Sadeep, Thio Chloe L, Goedert James J, Donfield Sharyne M, Kirk Gregory D, Thomas David L, O'Brien Stephen J, Smith Michael W
Laboratory of Genomic Diversity, National Cancer Institute, Frederick, MD, USA.
Int J Immunogenet. 2008 Jun;35(3):255-64. doi: 10.1111/j.1744-313X.2008.00770.x.
Hepatitis B virus (HBV) infection remains a serious global health problem despite the availability of a highly effective vaccine. Approximately 5% of HBV-infected adults develop chronic hepatitis B, which may result in liver cirrhosis or hepatocellular carcinoma. Variants of interleukin-10 (IL10) have been previously associated with chronic hepatitis B infection and progression to hepatocellular carcinoma. Single nucleotide polymorphisms (SNP; n = 42) from the IL10, IL19 and IL20 gene regions were examined for an association with HBV infection outcome, either chronic or recovered, in a nested case-control study of African Americans and European Americans. Among African Americans, three nominally statistically significant SNP associations in IL10, two in IL20, and one haplotype association were observed with different HBV infection outcomes (P = 0.005-0.04). A SNP (rs1518108) in IL20 deviated significantly from Hardy-Weinberg equilibrium in African Americans, with a large excess of heterozygotes in chronic HBV-infected cases (P = 0.0006), which suggests a strong genetic effect. Among European Americans, a nominally statistically significant SNP association in IL20 and an IL20 haplotype were associated with HBV recovery (P = 0.01-0.04). These results suggest that IL10 and IL20 gene variants influence HBV infection outcome and encourage the pursuit of further studies of these cytokines in HBV pathogenesis.
尽管已有高效疫苗，但乙型肝炎病毒（HBV）感染仍是一个严重的全球健康问题。约5%的HBV感染成年人会发展为慢性乙型肝炎，这可能导致肝硬化或肝细胞癌。白细胞介素-10（IL10）的变体先前已与慢性乙型肝炎感染及向肝细胞癌的进展相关联。在一项针对非裔美国人和欧裔美国人的巢式病例对照研究中，对IL10、IL19和IL20基因区域的单核苷酸多态性（SNP；n = 42）与HBV感染结果（慢性或康复）之间的关联进行了检测。在非裔美国人中，观察到IL10中有三个名义上具有统计学意义的SNP关联、IL20中有两个以及一个单倍型关联与不同的HBV感染结果相关（P = 0.005 - 0.04）。IL20中的一个SNP（rs1518108）在非裔美国人中显著偏离哈迪-温伯格平衡，慢性HBV感染病例中的杂合子大量过剩（P = 0.0006），这表明存在强大的遗传效应。在欧裔美国人中，IL20中的一个名义上具有统计学意义的SNP关联和一个IL20单倍型与HBV康复相关（P = 0.01 - 0.04）。这些结果表明，IL10和IL20基因变体影响HBV感染结果，并鼓励对这些细胞因子在HBV发病机制中的作用进行进一步研究。
