EBNA1 and LMP1 variants in multiple sclerosis cases and controls.
BACKGROUND
Prior infection with Epstein-Barr virus (EBV) is an established risk factor for multiple sclerosis (MS). Some findings from observational studies, including possible epidemics and differences in prevalence, may be explained if different strains of EBV conferred different MS risk.


METHODS
DNA was extracted from peripheral lymphocytes obtained from 66 MS cases and 66 age- and cohort-matched controls. Nested polymerase chain reaction (PCR) was performed to amplify the N- and C-terminus regions of EBNA1 and the hyper-variable region of the LMP1 gene. For EBNA1, we compared the presence of the prototype B95.8 vs variant sequence and the presence of multiple strains in MS cases and controls. For LMP1, we considered differences in the proportions of mutations between cases and controls.


RESULTS
Comparing the proportion of mutant sequence between MS cases and controls in the EBNA1 N-terminal (0/28 vs 1/27) and C-terminal regions (3/40 vs 8/36) revealed no significant differences (P > 0.05). No individual variants in LMP1 were associated with risk of MS (all P > 0.05). Neither EBNA1 nor LMP1 variation was associated with anti-EBNA1 IgG antibody titers.


CONCLUSIONS
These findings do not support a strong role for variation in EBNA1 N-terminus, EBNA1 C-terminus or LMP1 contributing to MS risk.
Simon
K C
KC
Department of Nutrition, Harvard School of Public Health, Boston, MA, USA. ksimon@hsph.harvard.edu
Yang
X
X
Munger
K L
KL
Ascherio
A
A
D000328:Adult; D016022:Case-Control Studies; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000276:immunology / Q000821:virology*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology; D006801:Humans; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology / Q000821:virology*; D014763:Viral Matrix Proteins / Q000235:genetics*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; D014763:Viral Matrix Proteins; C417029:EBV-encoded nuclear antigen 1