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APOE genotype is associated with oral herpetic lesions but not genital or oral herpes simplex virus shedding
  1. David M Koelle1,2,3,4,5,
  2. Amalia Magaret2,5,
  3. Terri Warren6,
  4. Gerard D Schellenberg7,
  5. Anna Wald1,2,5,8
  1. 1Department of Medicine, University of Washington, Seattle, Washington, USA
  2. 2Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA
  3. 3Department of Global Health Medicine, University of Washington, Seattle, Washington, USA
  4. 4Benaroya Research Institute, Seattle, Washington, USA
  5. 5Vaccine and Infectious Diseases Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
  6. 6Westover Heights Clinic, Portland, Oregon, USA
  7. 7Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
  8. 8Department of Epidemiology, University of Washington, Seattle, Washington, USA
  1. Correspondence to Dr David M Koelle, University of Washington, 1616 Eastlake Avenue East, Suite 500, UW Mail Stop 358117, Seattle, WA 98102, USA; viralimm{at}


Background Apolipoprotein E is polymorphic in the human population. APOE4 has previously been reported to correlate with symptomatic oral and genital herpes disease.

Methods APOE was genotyped in 182 subjects with herpes simplex virus (HSV) 2 and in 62 subjects with HSV-1, including 44 subjects with both viral types for a total of 200 adults. HSV shedding was measured by PCR from swab samples obtained daily from mucosa for at least 30 days. Participants also maintained a diary of oral or genital lesions.

Results The APOE genotypes observed reflected the US white population and the Hardy–Weinberg equilibrium. Genital and oral HSV shedding was detected on 17.2% and 3.7% of overall days, respectively, whereas genital and oral lesion rates were 10.1% and 2.9%. Using Poisson regression and adjusting for known correlates of HSV shedding, a significant association was not observed between the APOE genotype and genital or oral HSV shedding, or genital HSV lesions. However, the presence of the APOE4 allele was associated with a higher rate of oral herpetic lesions, with a relative risk of 4.64 (95% CI 1.32 to 15.05, p=0.016).

Conclusions Variation at the APOE locus may be associated with clinical manifestations of HSV-1 infection, but does not appear to correlate with herpes simplex viral reactivation in humans.

  • Apolipoprotein E
  • genital herpes
  • genotype
  • herpes
  • herpes simplex virus
  • PCR
  • viral shedding

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  • Funding Funding was provided by National Institutes of Health grants U19 AI031448 and PO1 AI30731.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the University of Washington and Western Institutional Review Board.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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