title: Role of the human endogenous retrovirus HERV-K18 in autoimmune disease susceptibility: study in the Spanish population and meta-analysis.
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: p(M-H) = 0.0008; OR(M-H) (95% CI) = 1.22 (1.09-1.38)].
  
  
  CONCLUSIONS
  Association of the HERV-K18.3 haplotype in chromosome 1 with autoimmune-disease susceptibility was confirmed through meta-analysis.
authors: Immunology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Madrid, Spain.
authors: Belén
authors: B
authors: de la Hera
authors: Jezabel
authors: J
authors: Varadé
authors: Marta
authors: M
authors: García-Montojo
authors: José Ramón
authors: JR
authors: Lamas
authors: Ana
authors: A
authors: de la Encarnación
authors: Rafael
authors: R
authors: Arroyo
authors: Benjamín
authors: B
authors: Fernández-Gutiérrez
authors: Roberto
authors: R
authors: Alvarez-Lafuente
authors: Elena
authors: E
authors: Urcelay
mesh_terms: D000328:Adult; D001327:Autoimmune Diseases / Q000821:virology*; D004198:Disease Susceptibility / Q000821:virology; D020077:Endogenous Retroviruses / Q000235:genetics / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013030:Spain
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