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


METHODS
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.
Alvarez-Lafuente
R
R
Servicio de Neurología, Hospital Clínico San Carlos, Madrid, Spain. ralvarezlafuente@yahoo.es
Martinez
A
A
Garcia-Montojo
M
M
Mas
A
A
De Las Heras
V
V
Dominguez-Mozo
M I
MI
Maria Del Carmen
C
C
López-Cavanillas
M
M
Bartolome
M
M
Gomez de la Concha
E
E
Urcelay
E
E
Arroyo
R
R
D000328:Adult; D004252:DNA Mutational Analysis; D004777:Environment; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D015654:Herpesvirus 6, Human / Q000235:genetics*; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics* / Q000503:physiopathology / Q000821:virology*; D009687:Nuclear Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D019349:Roseolovirus Infections / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*; D014779:Virus Replication / Q000235:genetics*; D055815:Young Adult
C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators; D016899:Interferon-beta