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

¹ Department of Pathology, Tufts University School of Medicine, Boston, Massachusetts, USA
² Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA
³ Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA; Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA; Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA

^* To whom correspondence should be addressed.

	Abstract

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 (2 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.

Key Words: endogenous retroviruses, HERV-K18, HLA, multiple sclerosis, polymorphisms

First published on August 13, 2008, doi:10.1177/1352458508094641

Multiple Sclerosis 2008;14:1175.

A more recent version of this article appeared on November 1, 2008


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