title: The association between human endogenous retroviruses and multiple sclerosis: A systematic review and meta-analysis.
abstract: BACKGROUND
  The interaction between genetic and environmental factors is crucial to multiple sclerosis (MS) pathogenesis. Human Endogenous Retroviruses (HERVs) are endogenous viral elements of the human genome whose expression is associated with MS.
  
  
  OBJECTIVE
  To perform a systematic review and meta-analysis and to assess qualitative and quantitative evidence on the expression of HERV families in MS patients.
  
  
  METHODS
  Medline, Embase and the Cochrane Library were searched for published studies on the association of HERVs and MS. Meta-analysis was performed on the HERV-W family. Odds Ratio (OR) and 95% confidence interval (CI) were calculated for association.
  
  
  RESULTS
  43 reports were extracted (25 related to HERV-W, 13 to HERV-H, 9 to HERV-K, 5 to HRES-1 and 1 to HER-15 family). The analysis showed an association between expression of all HERV families and MS. For HERV-W, adequate data was available for meta-analysis. Results from meta-analyses of HERV-W were OR = 22.66 (95%CI 6.32 to 81.20) from 4 studies investigating MSRV/HERV-W (MS-associated retrovirus) envelope mRNA in peripheral blood mononuclear cells, OR = 44.11 (95%CI 12.95 to 150.30) from 6 studies of MSRV/HERV-W polymerase mRNA in serum/plasma and OR = 6.00 (95%CI 3.35 to 10.74) from 4 studies of MSRV/HERV-W polymerase mRNA in CSF.
  
  
  CONCLUSIONS
  This systematic review and meta-analysis shows an association between expression of HERVs, and in particular the HERV-W family, and MS.
authors.affiliation: Division of Clinical Neuroscience, University of Nottingham School of Medicine, Nottingham, Nottingham, United Kingdom.
authors.forename: Elena
authors.initials: E
authors.lastname: Morandi
authors.affiliation: Division of Clinical Neuroscience, University of Nottingham School of Medicine, Nottingham, Nottingham, United Kingdom.|Division of Clinical Neurosciences, University of Medicine and Pharmacy Carol Davila, Department of Neurology, Colentina Hospital, Bucharest, Romania.
authors.forename: Radu
authors.initials: R
authors.lastname: Tanasescu
authors.affiliation: University of Nottingham School of Veterinary Medicine and Science, Nottingham, United Kingdom.
authors.forename: Rachael E
authors.initials: RE
authors.lastname: Tarlinton
authors.affiliation: Division of Clinical Neuroscience, University of Nottingham School of Medicine, Nottingham, Nottingham, United Kingdom.|Department of Neurology, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom.
authors.forename: Cris S
authors.initials: CS
authors.lastname: Constantinescu
authors.affiliation: Division of Rheumatology, Orthopaedics and Dermatology, University of Nottingham School of Medicine, Nottingham, United Kingdom.
authors.forename: Weiya
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Division of Clinical Neuroscience, University of Nottingham School of Medicine, Nottingham, Nottingham, United Kingdom.
authors.forename: Christopher
authors.initials: C
authors.lastname: Tench
authors.affiliation: Division of Clinical Neuroscience, University of Nottingham School of Medicine, Nottingham, Nottingham, United Kingdom.|Department of Neurology, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom.
authors.forename: Bruno
authors.identifier: http://orcid.org/0000-0001-6384-2342
authors.initials: B
authors.lastname: Gran
mesh_terms: D020077:Endogenous Retroviruses / Q000472:pathogenicity*; D006801:Humans; D009103:Multiple Sclerosis / Q000821:virology*