MHC2TA rs4774C and HHV-6A active replication in multiple sclerosis patients

Background and purpose: In a previous report, a strong gene-environment interaction between human herpesvirus 6A (HHV6A) active replication and MHC2TA rs4774C was demonstrated. The objectives of this study were: (i) to reappraise the association that was found in the previous study; (ii) to evaluate if MS patients with minor allele C and HHV-6A active infection had different clinical behavior; and (iii) to analyze the possible association of MHC2TA rs4774C with Epstein-Barr virus (EBV). Methods: A total of 149 MS patients were analyzed both at the MHC2TA locus and by HHV-6A status in serum. We studied a G/C polymorphism (rs4774) by a TaqMan Assay-on-Demand. HHV-6A genomes in serum were evaluated by quantitative PCR. A control group of 562 healthy Spanish individuals was included for comparative purposes in the genetic analyses. A battery of clinical data was collected for all the MS patients included in the study. Results: (i) MHC2TA/HHV-6A interaction: we found the same strong association of the rs4774C allele with HHV-6A active replication than in the previous study (P = 0.0001). (ii) Clinical data: the two main statistical significant differences for MS patients with HHV-6A active infection and minor allele C were: (a) a significant number of them were not free of progression (EDSS = 0) 2 years after the diagnosis (P = 0.01); (b) only a third of them responded to interferon beta treatment (P = 0.05). Conclusions: This study has verified previous results about the strong gene-environment interaction between HHV6A active replication and MHC2TA rs4774C. Furthermore, a different clinical behavior for MS patients with HHV-6A active infection and minor allele C was found.