Role of the Human Endogenous Retrovirus HERV-K18 in Autoimmune Disease Susceptibility: Study in the Spanish Population and Meta-Analysis

Belén de la Hera, Jezabel Varadé, Marta García-Montojo, José Ramón Lamas, Ana de la Encarnación, Rafael Arroyo, Benjamín Fernández-Gutiérrez, Roberto Álvarez-Lafuente and Elena Urcelay

PLOS ONE, 2013, vol. 8, issue 4, 1-7

Abstract: 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: pM-H = 0.0008; ORM-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.

Date: 2013
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0062090 (text/html)
https://journals.plos.org/plosone/article/file?id= ... 62090&type=printable (application/pdf)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0062090

DOI: 10.1371/journal.pone.0062090

Access Statistics for this article

More articles in PLOS ONE from Public Library of Science
Bibliographic data for series maintained by plosone ().