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Meta-Analysis
. 2017 Feb 16;12(2):e0172415.
doi: 10.1371/journal.pone.0172415. eCollection 2017.

The association between human endogenous retroviruses and multiple sclerosis: A systematic review and meta-analysis

Elena Morandi  1 , Radu Tanasescu  1   2 , Rachael E Tarlinton  3 , Cris S Constantinescu  1   4 , Weiya Zhang  5 , Christopher Tench  1 , Bruno Gran  1   4
Affiliations
Meta-Analysis

The association between human endogenous retroviruses and multiple sclerosis: A systematic review and meta-analysis

Elena Morandi et al. PLoS One. .

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Genetic structure of HERVs.
LTRs (Long Terminal Repeat) regions bound the genome with four major viral genes: gag (encoding matrix and retroviral core), pol (reverse transcriptase and integrase), pro (protease), and env (envelope).
Fig 2
Fig 2. Flow chart of the study selection and procedure.
Articles identified and selected for the qualitative and quantitative synthesis.
Fig 3
Fig 3. Summary meta-analysis.
Forest plot and bias assessment funnel plot of comparison of the expression of (A) MSRV/HERV-Wenv in PBMC, (B) MSRV/HERV-Wpol in serum/plasma, and (C) MSRV/HERV-Wpol in CSF in MS patients vs controls.
See this image and copyright information in PMC

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