Journal
MULTIPLE SCLEROSIS JOURNAL
Volume 14, Issue 9, Pages 1175-1180Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1177/1352458508094641
Keywords
endogenous retroviruses; HERV-K18; HLA; multiple sclerosis; polymorphisms
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Funding
- NIH/NINDS [RO1 N504767]
- National Multiple Sclerosis Society to BTH
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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 (chi 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. Multiple Sclerosis 2008; 14: 1175-1180. http://msj.sagepub.com
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