title: Interaction between RANTES promoter variant and CCR5Delta32 favors recovery from hepatitis B.
abstract: Recovery from acute hepatitis B virus (HBV) infection occurs in 95% of adult-acquired infections. A 32-bp deletion in CCR5 (CCR5Delta32), which encodes for a nonfunctional receptor, increases the likelihood of recovery. Using 181 subjects with persistent HBV infection and 316 who had recovered, we tested the hypothesis that an epistatic interaction between functional polymorphisms in RANTES (a CCR5 ligand) and CCR5 impacts recovery. Specific models designed to assess individual contributions of compound genotypes demonstrated that the only combination associated with recovery from an HBV infection was RANTES -403A with CCR5Delta32 (odds ratio 0.36, p = 0.02). Because the phenotypic consequence of -403A is reported to be higher levels of RANTES, we propose a model in which excess RANTES in combination with low CCR5 favors recovery from an HBV infection, which will require validation through functional testing.
authors.affiliation: Department of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
authors.forename: Chloe L
authors.initials: CL
authors.lastname: Thio
authors.forename: Jacquie
authors.initials: J
authors.lastname: Astemborski
authors.forename: Rasmi
authors.initials: R
authors.lastname: Thomas
authors.forename: Timothy
authors.initials: T
authors.lastname: Mosbruger
authors.forename: Mallory D
authors.initials: MD
authors.lastname: Witt
authors.forename: James J
authors.initials: JJ
authors.lastname: Goedert
authors.forename: Keith
authors.initials: K
authors.lastname: Hoots
authors.forename: Cherie
authors.initials: C
authors.lastname: Winkler
authors.forename: David L
authors.initials: DL
authors.lastname: Thomas
authors.forename: Mary
authors.initials: M
authors.lastname: Carrington
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D001483:Base Sequence / Q000235:genetics*; D018946:Chemokine CCL5 / Q000235:genetics* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004843:Epistasis, Genetic / Q000235:genetics / Q000276:immunology; D005260:Female; D006509:Hepatitis B / Q000235:genetics* / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D006801:Humans; D008297:Male; D008957:Models, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics* / Q000276:immunology; D019713:Receptors, CCR5 / Q000235:genetics* / Q000276:immunology; D017384:Sequence Deletion / Q000235:genetics* / Q000276:immunology; D014481:United States
chemical_list: C483024:CCL5 protein, human; D018946:Chemokine CCL5; D019713:Receptors, CCR5