Variation of the myelin oligodendrocyte glycoprotein gene is not primarily associated with multiple sclerosis in the Sardinian population.
BACKGROUND
Multiple sclerosis (MS) is consistently associated with particular HLA-DRB1-DQB1 haplotypes. However, existing evidence suggests that variation at these loci does not entirely explain association of the HLA region with the disease. The MOG locus is a prime positional and functional candidate for such additional predisposing effects but the analysis is complicated by the strong, albeit labyrinthine pattern of linkage disequilibrium in the region. Here we have assessed the association of MOG variation with MS in the Sardinian population to see if it represents an independent contributor to MS predisposition.


RESULTS
After re-sequencing the MOG gene in 21 healthy parents of MS patients we detected 134 variants, 33 of which were novel. A set of 40 informative SNPs was then selected and assessed for disease association together with 1 intragenic microsatellite in an initial data set of 239 MS families. This microsatellite and 11 SNPs were found to be positively associated with MS, using the transmission disequilibrium test, and were followed up in an additional 158 families (total families analysed = 397). While in these 397 families, 8 markers showed significant association with MS, through conditional tests we determined that these MOG variants were not associated with MS independently of the main DRB1-DQB1 disease associations.


CONCLUSIONS
These results indicate that variation within the MOG gene is not an important independent determinant of MS-inherited risk in the Sardinian population.
Marrosu
Maria Giovanna
MG
Centro Sclerosi Multipla, Dipartimento di Scienze Neurologiche e Cardiovascolari, University of Cagliari, Italy. gmarrosu@unica.it <gmarrosu@unica.it>
Murru
Raffaele
R
Costa
Gianna
G
Melis
Maria Cristina
MC
Rolesu
Marcella
M
Schirru
Lucia
L
Solla
Elisabetta
E
Cuccu
Stefania
S
Secci
Maria Antonietta
MA
Whalen
Michael B
MB
Cocco
Eleonora
E
Pugliatti
Maura
M
Sotgiu
Stefano
S
Rosati
Giulio
G
Cucca
Francesco
F
D000293:Adolescent; D000328:Adult; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007558:Italy; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics*; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000235:genetics*; D063308:Myelin-Oligodendrocyte Glycoprotein; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044465:White People / Q000235:genetics*
C571326:MOG protein, human; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein