title: Interferon Lambda 4 Genotype Is Not Associated with Recurrence of Oral or Genital Herpes.
abstract: IFNL4-ΔG/TT (rs368234815) genotype is associated with hepatitis C virus clearance and may play a role in other infections. IFN-λ4 protein is generated only in individuals who carry the IFNL4-ΔG allele. The IFNL4 rs12979860-T allele, which is in strong linkage disequilibrium with IFNL4-ΔG, was recently reported to be associated with more frequent and severe oral herpes episodes. We investigated the association of IFNL4-ΔG/TT with herpes simplex virus (HSV)-related outcomes among 2,192 African American and European American participants in the Women's Interagency HIV Study (WIHS). WIHS is a prospective cohort study of human immunodeficiency virus (HIV)-infected and at-risk women that began in 1994. This report includes follow-up through 2013. Available data included: HSV-1 and HSV-2 antibodies at study entry; bi-annually ascertained episodes of (self-reported) oral herpes, (self-reported) genital sores and (clinician-observed) genital ulcers; HSV-2 DNA in cervicovaginal lavage (CVL) specimens. IFNL4-ΔG/TT genotyping was determined by TaqMan. We compared women with IFNL4-ΔG/ΔG or IFNL4-TT/ΔG genotypes (i.e., IFNL4-ΔG carriers) to those with the IFNL4-TT/TT genotype, adjusting for age, race and HIV status. For outcomes with repeated measurements, the adjusted odds ratio (aOR), 95% confidence interval [CI] and p-value were determined using a generalized estimating equations approach. Median participant age at enrollment was 36 years; 81% were African American, 74% were HIV-infected. Among 1,431 participants tested for antibodies, 72.8% were positive for HSV-1 and 79.0% were positive for HSV-2. We observed no association between IFNL4-ΔG/TT genotype and any outcome: HSV-1 or HSV-2 antibody prevalence (p>0.1, all comparisons); oral herpes (aOR, 1.2; p = 0.35); genital sores (aOR, 1.0; p = 0.71); genital ulcers (aOR, 1.1; p = 0.53); detectable HSV-2 DNA in CVL (N = 322; aOR, 0.71; p = 0.49); HSV-2 DNA level (p = 0.68). In this large prospective study, IFNL4-ΔG/TT genotype was not associated with HSV-related outcomes, including episodes of oral or genital herpes.
authors.affiliation: Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, United States of America.
authors.forename: Krystle A
authors.initials: KA
authors.lastname: Lang Kuhs
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Kuniholm
authors.affiliation: Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, United States of America.
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Pfeiffer
authors.affiliation: Information Management Services, Calverton, Maryland, United States of America.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Immunology and Microbiology, Rush University Medical Center, Chicago, Illinois, United States of America.
authors.forename: Seema
authors.initials: S
authors.lastname: Desai
authors.affiliation: Institute for Infectious Disease Research, National Development and Research Institutes, New York, New York, United States of America.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Edlin
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Marion G
authors.initials: MG
authors.lastname: Peters
authors.affiliation: Division of Infectious Diseases, Georgetown University Medical Center, Washington, D.C., United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Plankey
authors.affiliation: Epidemiology Branch, Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, United States of America.
authors.forename: Gerald B
authors.initials: GB
authors.lastname: Sharp
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors.forename: Howard D
authors.initials: HD
authors.lastname: Strickler
authors.affiliation: Department of Pediatrics, University of Southern California, Los Angeles, California, United States of America.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Villacres
authors.affiliation: Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, United States of America.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Quinn
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Gange
authors.affiliation: Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda Maryland, United States of America.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Prokunina-Olsson
authors.affiliation: Departments of Clinical Pharmacy, Medicine, Epidemiology, and Biostatistics, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Greenblatt
authors.affiliation: Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, United States of America.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: O'Brien
mesh_terms: D000328:Adult; D005260:Female; D005838:Genotype; D006558:Herpes Genitalis / Q000235:genetics / Q000473:pathology*; D006560:Herpes Labialis / Q000235:genetics / Q000473:pathology*; D006801:Humans; D007378:Interleukins / Q000235:genetics*; D011446:Prospective Studies; D012008:Recurrence; D000095022:Interferon Lambda
chemical_list: D007378:Interleukins; C579163:IFNL4 protein, human; D000095022:Interferon Lambda