Herpesvirus active replication in multiple sclerosis: a genetic control?

Although the etiology of multiple sclerosis (MS) is unknown, it is generally believed that genetic, immunologic, and environmental factors are involved. The objectives of this study were: 1. to analyze if a genetic control could explain why HHV-6 would be able to actively replicate in a subset of MS patients but not in controls; 2. to study if MS patients with HHV-6 active replication are clinically different from those without HHV-6 active replication. A total of 195 MS patients and 195 controls were analyzed for two SNPs at the MHC2TA locus and two SNPs at the CD46 locus. Furthermore, the MS cohort was analyzed by PCR for the detection of HHV-6 genomes in five serum samples collected every six months along two-year follow-up. We found that 59/195 (30.2%) MS patients had at least one HHV-6 positive serum sample. No statistical significant difference was found for the two genes when the comparison was made between MS patients and controls; however, a statistical significance was found for the two polymorphisms of MHC2TA when we compared MS patients with active replication and controls (p=0.0000004 for rs4774C and p=0.011 for rs3087456G). Furthermore, increased significant differences were found for MHC2TA and CD46 when we compared interferon beta responders and non-responders within MS patients. In conclusion, we describe a gene-environment interaction in MS patients between HHV-6 and MHC2TA and CD46 that should be further studied to clarify if that interaction could be a genetic control. The results show that MS patients without HHV-6 active replication are better responders to interferon beta treatment than those with HHV-6 active replication.

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