Characteristic imprint of single nucleotide polymorphisms in multiple sclerosis.
Although the main pathomechanism of multiple sclerosis (MS) is not known, an autoimmune response against the myelin basic proteins (MBPs) is presumed to be involved in its evolution and propagation. In this study, we examined whether the nucleotide sequences of the 3' untranslated regions (UTRs) of the DNAs encoding the MBP are characteristic of MS. These genetic regions are presumed to be responsible for the transport and localization of the mRNAs encoding the MBP in the glia cells, thereby influencing the building up of the myelin sheaths of the glia cells. The DNA region involving nucleotides 710-1540 of the UTRs of the MBPs was sequenced and analyzed in 52 relapsing-remitting MS patients, in 52 neuroimaging alteration-free controls, and in 45 healthy volunteers. Although the examined UTRs exhibited a wide range of sequence variations in both the MS and the control subjects, we found a typical distribution of single nucleotide polymorphisms (SNPs) along the examined DNA sequence in the MS patients, which was different from that in the controls. We could distinguish two genetic regions: region A--nucleotide positions 851-896 and B--nucleotide positions 897-1540, in the UTRs. Subjects with SNPs in region A but without SNPs in region B occurred significantly more frequently in the MS group than in the control group (30.8% versus 3.85%, p < 0.0002848, OR 11.11, 95% CI--2.4-51.4, p < 0.0004). The distribution pattern of the SNPs in the UTRs seems to be highly characteristic of relapsing-remitting MS. These findings call attention to the possible roles of the UTRs of the MBPs in the development of MS.
Szolnoki
Zoltan
Z
Department of Cerebrovascular Diseases, Pándy Kálmán County Hospital, Gyula, Hungary. szolnoki99@hotmail.com
Kondacs
Andras
A
Mandi
Yvette
Y
Somogyvari
Ferenc
F
D000328:Adult; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics* / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA