Wozniak Matthew A, Shipley Suzanne J, Dobson Curtis B, Parker Simon P, Scott Fiona T, Leedham-Green Mary, Breuer Judy, Itzhaki Ruth F
Faculty of Life Sciences, The University of Manchester, Manchester, UK.
Eur J Hum Genet. 2007 Jun;15(6):672-8. doi: 10.1038/sj.ejhg.5201812. Epub 2007 Mar 14.
Over 90% of the population are infected with varicella zoster virus (VZV) but only some develop shingles - caused when the virus reactivates from latency, and only some shingles patients develop post-herpetic neuralgia (PHN), defined as pain continuing for more than about 4 months. Epstein Barr virus (EBV) similarly infects over 90% of the population; some of those infected during teenage or young adult years develop infectious mononucleosis (IM). The reason for these disparities between numbers infected and numbers affected by illness is unknown, but presumably reflects host factor(s). Our previous results showed that apolipoprotein E (APOE) genotype determines susceptibility to, or outcome of, infection in the case of several diseases of known infectious cause. Therefore, we investigated APOE genotypes of shingles, PHN, and IM patients. Our rationale for the previous studies and for investigating VZV was that these micro-organisms use for cell binding and entry the same sites in the cell surface as does the protein apoE, and that consequently, competition with apoE could affect the pathogen's extent of entry and hence extent of the damage caused. The APOE genotypes of shingles and PHN sufferers, and of IM sufferers were determined using restriction fragment length polymorphism. In females, epsilon4 homozygosity confers a risk of shingles and also of IM, and the APOE-epsilon4 allele is protective against PHN whereas APOE-epsilon3 allele is a risk. Our results showing that a host genetic factor influences the development of shingles and PHN in females have clinical significance: they could lead to identification of those (female) patients at greater risk of PHN, thus enabling these people to be targeted for treatment with the most effective drugs.
超过90%的人群感染过水痘带状疱疹病毒（VZV），但只有一部分人会患上带状疱疹——这是由该病毒从潜伏状态重新激活所致，而且只有部分带状疱疹患者会发展为带状疱疹后神经痛（PHN），即疼痛持续超过约4个月。爱泼斯坦-巴尔病毒（EBV）同样感染超过90%的人群；其中一些在青少年或青年时期感染的人会患上传染性单核细胞增多症（IM）。感染人数与患病受影响人数之间存在这些差异的原因尚不清楚，但推测反映了宿主因素。我们之前的研究结果表明，载脂蛋白E（APOE）基因型在几种已知感染病因的疾病中决定了易感性或感染结果。因此，我们调查了带状疱疹、PHN和IM患者的APOE基因型。我们之前研究以及对VZV进行研究的基本原理是，这些微生物用于细胞结合和进入细胞表面的位点与载脂蛋白E相同，因此，与载脂蛋白E的竞争可能会影响病原体的进入程度，进而影响所造成的损害程度。使用限制性片段长度多态性方法确定了带状疱疹和PHN患者以及IM患者的APOE基因型。在女性中，ε4纯合性会增加患带状疱疹和IM的风险，而APOE-ε4等位基因对PHN具有保护作用，而APOE-ε3等位基因则会增加患病风险。我们的结果表明宿主遗传因素会影响女性带状疱疹和PHN的发病，这具有临床意义：它们可能会有助于识别那些（女性）患PHN风险更高的患者，从而使这些人能够成为使用最有效药物进行治疗的目标人群。
