The Effect of HLA, IL2RA and IL7RA Alleles on the Risk of Multiple Sclerosis in HHV-6 Infected and Uninfected Lebanese Subjects

Abstract

Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system. We have previously demonstrated that an HHV-6 infection increases the risk of MS and that particular single nucleotide polymorphisms (SNPs) in the IL2RA and IL7RA genes modestly enhance the risk of this disease in HHV-6 positive subjects. To assess whether human leukocyte antigen (HLA) genetic determinants affect the risk of susceptibility to MS, blood samples were collected from 41 MS patients and 38 controls. Subject HLA genetic profiles were then determined by DNA sequence specific primers (SSP) typing. Detection of HHV-6 DNA was carried out using nested PCR while IL2RA and IL7RA allele detection was performed using restriction fragment length polymorphism (RFLP) analysis. We observed an increase in the risk of susceptibility to MS in individuals harboring the A*2301 (p=0.033) and the A*0301 (p=0.032) HLA alleles. Double positivity for the DQB1*0501 allele and HHV-6 enhanced the risk of this disease (p=0.036) while DQB1*0501 positivity by itself was not associated with the disorder. Combinational positivity for the IL2RA and IL7RA SNPs, HHV-6 in addition to the various HLA alleles did not result in significant MS risk increases in our study population. Hence, particular genetic determinants increase the risk of MS in HHV-6 positive subjects. These determinants do not exert the same effects in uninfected individuals.