Specific retroviral sequences in our genomes increase our risk of developing MS. #MSBlog #MSResearch
de la Hera et al. 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
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. This study 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.
“This study suggests that variations in the sequence of a virus that resides in our genome increases your risk of MS and other autoimmune diseases. Interesting? The majority of studies of this nature are not replicated and turn-out to be false positive. If this study is replicated then it suggest that this variation is linked to something in the genome that increases your risk of MS. How this does this will need to be evaluated biologically using various experimental methods. Is this study important? Possibly it adds to the potential complexity of MS and provides further arguments for including HERVs in our thinking about MS. In addition, this provides support for targeting HERVs as a potential treatment for MS.”