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

• Published in: European journal of neurology Vol. 17; no. 1; pp. 129 - 135
• Main Authors: Alvarez-Lafuente, R., Martinez, A., Garcia-Montojo, M., Mas, A., De Las Heras, V., Dominguez-Mozo, M. I., Maria del Carmen, C., López-Cavanillas, M., Bartolome, M., Gomez de la Concha, E., Urcelay, E., Arroyo, R.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-01-2010; John Wiley & Sons, Inc
• Subjects: Adult; clinical behavior; DNA Mutational Analysis; Environment; Epstein-Barr virus; Female; Gene Frequency - genetics; Genes; Genetic Predisposition to Disease - genetics; Genetic Testing; Herpesvirus 6, Human - genetics; HHV-6; Human herpesvirus; Humans; Infections; Interferon-beta - pharmacology; Interferon-beta - therapeutic use; Male; MHC2TA; Middle Aged; Multiple Sclerosis - genetics; Multiple Sclerosis - physiopathology; Multiple Sclerosis - virology; Nuclear Proteins - genetics; Polymorphism, Genetic - genetics; quantitative PCR; Roseolovirus Infections - genetics; Trans-Activators - genetics; Virus Replication - genetics; Young Adult
• ISSN: 1351-5101; 1468-1331
• DOI: 10.1111/j.1468-1331.2009.02758.x

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.