title: Human endogenous retrovirus-K18 Env as a risk factor in multiple sclerosis.
abstract: BackgroundThe 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.ObjectiveTo assess whether variation in HERV-K18 Env is a risk factor for MS.MethodsWe 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.ResultsOverall, there was a significant association between HERV-K18 env genotype and MS risk (chi2 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).ConclusionVariation in EBV-associated superantigen HERV-K18 Env could influence the genetic susceptibility to MS.
authors.affiliation: Department of Pathology, Tufts University School of Medicine, Boston, Massachusetts, USA.
authors.forename: A K
authors.initials: AK
authors.lastname: Tai
authors.forename: E J
authors.initials: EJ
authors.lastname: O'Reilly
authors.forename: K A
authors.initials: KA
authors.lastname: Alroy
authors.forename: K C
authors.initials: KC
authors.lastname: Simon
authors.forename: K L
authors.initials: KL
authors.lastname: Munger
authors.forename: B T
authors.initials: BT
authors.lastname: Huber
authors.forename: A
authors.initials: A
authors.lastname: Ascherio
mesh_terms: D016022:Case-Control Studies; D020077:Endogenous Retroviruses / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000276:immunology; D009103:Multiple Sclerosis / Q000453:epidemiology / Q000276:immunology / Q000821:virology; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D018089:Superantigens / Q000235:genetics* / Q000276:immunology
chemical_list: C107453:ERVK-18 protein, human; D008565:Membrane Proteins; D018089:Superantigens