Human endogenous retrovirus-K18 Env as a risk factor in multiple sclerosis

• Published in: Multiple sclerosis Vol. 14; no. 9; pp. 1175 - 1180
• Main Authors: Tai, AK, O’Reilly, EJ, Alroy, KA, Simon, KC, Munger, KL, Huber, BT, Ascherio, A
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01-11-2008; Sage Publications; Sage Publications Ltd
• Subjects: Biological and medical sciences; Case-Control Studies; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Endogenous Retroviruses - genetics; Epstein-Barr virus; Genetic Predisposition to Disease - epidemiology; Genotype; Human endogenous retrovirus; Humans; Medical sciences; Membrane Proteins - genetics; Membrane Proteins - immunology; Multiple Sclerosis - epidemiology; Multiple Sclerosis - immunology; Multiple Sclerosis - virology; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Neurology; Polymorphism, Single Nucleotide; Risk Factors; Superantigens - genetics; Superantigens - immunology; endogenous retroviruses; HLA; polymorphisms; multiple sclerosis; HERV-K18; Human; HLA-System; Nervous system diseases; Multiple sclerosis; Inflammatory disease; Central nervous system disease; Risk factor; Degenerative disease; Polymorphism
• DOI: 10.1177/1352458508094641
• EISSN: 1477-0970
• ISSN: 1352-4585

Background
The human endogenous retrovirus (HERV)-K18 Env is an Epstein-Barr virus (EBV)-associated superantigen. Given the evidence for a role of EBV in the etiology of multiple sclerosis (MS), HERV-K18 Env is a plausible candidate for association with MS.
Objective
To assess whether variation in HERV-K18 Env is a risk factor for MS.
Methods
We developed a single nucleotide polymorphism-based genotyping method to determine the distribution of the three alleles of HERV-K18 env. We then conducted a nested case-control study including 207 MS cases and 403 matched controls. Analyses were replicated in an independent series of 909 MS cases and 339 controls.
Results
Overall, there was a significant association between HERV-K18 env genotype and MS risk (χ2 P = 0.03). As compared with K18.2/K18.2 individuals, risk of MS was three fold higher among K18.3/K18.3 individuals (P = 0.03). An increase in MS risk among carriers of the K18.3 allele was also observed in the replication study, but did not reach statistical significance. In pooled analyses, K18.3/K18.3 individuals had a significantly increased risk of MS (relative risks [RR] comparing K18.3/K18.3 vs K18.2/K18.2 = 2.7; 95% confidence interval: 1.1–6.4).
Conclusion
Variation in EBV-associated superantigen HERV-K18 Env could influence the genetic susceptibility to MS.