A Polymorphism Within the MBP Gene Is Associated With a Higher Relapse Number in Male Patients of Multiple Sclerosis.
FRONTIERS IN IMMUNOLOGY(2020)
Abstract
Myelin basic protein (MBP) is thought to be one of the key autoantigens in multiple sclerosis (MS) development. A recent study described the association of the single nucleotide polymorphism (SNP) rs12959006, within the MBP gene, with a higher risk of relapse and worse prognosis. We aim at studying potential associations of this SNP to MS in an independent population. Clinical data of the first 5 years of the disease were collected retrospectively from 291 MS confirmed patients. MBP polymorphism rs12959006 was genotyped in all patients. Associations with EDSS, number of relapses and serology for Herpesvirus 6 (HHV-6) and Epstein Barr (EBV) viruses were studied. Lymphocyte activation measured by CD69 expression was also analyzed according to sex and rs12959006 genotype. The rs12959006 polymorphism contributed significantly to a higher number of relapses at 5 years after onset only in male patients (rs12959006*TT beta = 0.74 [0.36-1.09]; p = 7 x 10(-5)). Titers of anti-HHV6 IgG antibodies showed also a mild association with relapses, both in male and female patients (beta = 0.01 [0.01-0.02]; p = 3.7 x 10(-8)). Both the genetic variation in MBP and HHV-6 infection aid in predicting a higher number of relapses during the first years of MS. The association described in MBP rs12959006*T is exclusive to male patients.
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Key words
multiple sclerosis,SNP,HHV-6,myelin basic protein,relapse,sex differences,genetic marker
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