Single nucleotide polymorphisms in or near human endogenous retroviral loci were significantly associated with autoimmune diseases, including a strong association between rs5993426 near HERV-K and rheumatoid arthritis (OR 2.87).
Case-Control
Yes
Are single nucleotide polymorphisms in human endogenous retroviral loci associated with multiple sclerosis, type 1 diabetes mellitus, and rheumatoid arthritis?
Specific human endogenous retroviral loci and their genetic interactions are associated with susceptibility to multiple sclerosis, type 1 diabetes mellitus, and rheumatoid arthritis, suggesting a potential role in autoimmune disease pathogenesis.
Odds Ratio: 2.87 (95% CI 2.07–3.99)
p-value: p=7x10^-13
Autoimmune diseases encompass a plethora of conditions in which the immune system attacks its own tissue, identifying them as foreign. Multiple factors are thought to contribute to the development of immune response to self, including differences in genotypes, hormonal milieu, and environmental factors. Viruses including human endogenous retroviruses have long been linked to the occurrence of autoimmunity, but never proven to be causative factors. Endogenous viruses are retroviral sequences embedded in the host germline DNA and transmitted vertically through successive generations in a Mendelian manner. In this study by means of genetic epidemiology, we have searched for the involvement of endogenous retroviruses in three selected autoimmune diseases: multiple sclerosis, type 1 diabetes mellitus, and rheumatoid arthritis. We found that at least one human endogenous retroviral locus was associated with each of the three diseases. Although there was a significant overlap, most loci only occurred in one of the studied disease. Remarkably, within each disease, there was a statistical interaction (synergy) between two loci. Additional synergy between retroviral loci and human lymphocyte antigens is reported for multiple sclerosis. We speculate the possibility that recombinants or mixed viral particles are formed and that the resulting viruses stimulate the innate immune system, thereby initiating the autoimmune response.
Nexø et al. (2015) conducted a case-control in Autoimmune diseases (Multiple sclerosis, Type 1 diabetes mellitus, Rheumatoid arthritis). Single nucleotide polymorphisms in or near human endogenous retroviral loci vs. Alternative alleles / healthy controls was evaluated on Association of rs5993426 (G-allele) near HERV-K with rheumatoid arthritis (OR 2.87, 95% CI 2.07-3.99, p=7x10^-13). Single nucleotide polymorphisms in or near human endogenous retroviral loci were significantly associated with autoimmune diseases, including a strong association between rs5993426 near HERV-K and rheumatoid arthritis (OR 2.87).