Role of the human endogenous retrovirus HERV-K18 in autoimmune disease susceptibility: study in the Spanish population and meta-analysis

PLoS One. 2013 Apr 25;8(4):e62090. doi: 10.1371/journal.pone.0062090. Print 2013.


Background: Human endogenous retroviruses (HERVs) are genomic sequences that resulted from ancestral germ-line infections by exogenous retroviruses and therefore are transmitted in a Mendelian fashion. Increased HERV expression and antibodies to HERV antigens have been found in various autoimmune diseases. HERV-K18 in chromosome 1 was previously associated with type one diabetes and multiple sclerosis (MS). The etiology of these complex conditions has not been completely elucidated even after the powerful genome wide association studies (GWAS) performed. Nonetheless, this approach does not scrutinize the repetitive sequences within the genome, and part of the missing heritability could lie behind these sequences. We aimed at evaluating the role of HERV-K18 in chromosome 1 on autoimmune disease susceptibility.

Methods: Two HERV-K18 SNPs (97Y/C and 154W/Stop substitutions) conforming three haplotypes were genotyped in Spanish cohorts of multiple sclerosis (n = 942), rheumatoid arthritis (n = 462) and ethnically matched controls (n = 601). Our findings were pooled in a meta-analysis including 5312 autoimmune patients and 4032 controls.

Results: Significant associations of both HERV-K18 polymorphisms in chromosome 1 with MS patients stratified by HLA-DRB1*15:01 were observed [97Y/C p = 0.02; OR (95% CI) = 1.5 (1.04-2.17) and 154W/Stop: p = 0.001; OR (95% CI) = 1.6 (1.19-2.16)]. Combined meta-analysis of the previously published association studies of HERV-K18 with different autoimmune diseases, together with data derived from Spanish cohorts, yielded a significant association of the HERV-K18.3 haplotype [97Y-154W: p(M-H) = 0.0008; OR(M-H) (95% CI) = 1.22 (1.09-1.38)].

Conclusion: Association of the HERV-K18.3 haplotype in chromosome 1 with autoimmune-disease susceptibility was confirmed through meta-analysis.

Publication types

  • Meta-Analysis

MeSH terms

  • Adult
  • Autoimmune Diseases / virology*
  • Disease Susceptibility / virology
  • Endogenous Retroviruses / genetics
  • Endogenous Retroviruses / physiology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Spain

Grants and funding

Belén de la Hera is recipient of a PhD scholarship from ‘Fondo de Investigaciones Sanitarias’ (FI11/00560), Jezabel Varadé is recipient of a contract from “Ministerio de Economía y Competitividad” (PTA2011-6137-1) and Elena Urcelay works for the Fundación para la Investigación Biomédica-Hospital Clínico San Carlos. Financial support for the study was provided by: Fondo de Investigaciones Sanitarias FEDER-FIS (grant numbers: PI08/1636 and PI10/1985) and Fundación Alicia Koplowitz. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.