HLA-class I markers and multiple sclerosis susceptibility in the Italian population

• Published in: Genes and immunity Vol. 11; no. 2; pp. 173 - 180
• Main Authors: Bergamaschi, L, Leone, M A, Fasano, M E, Guerini, F R, Ferrante, D, Bolognesi, E, Barizzone, N, Corrado, L, Naldi, P, Agliardi, C, Dametto, E, Salvetti, M, Visconti, A, Galimberti, D, Scarpini, E, Vercellino, M, Bergamaschi, R, Monaco, F, Caputo, D, Momigliano-Richiardi, P, D'Alfonso, S
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-03-2010; Nature Publishing Group
• Subjects: Alleles; Autoimmune diseases; Biomedical and Life Sciences; Biomedicine; Cancer Research; Confidence intervals; Demographic aspects; Disease Susceptibility - immunology; Gene Expression; Genes; Genetic aspects; Genetic markers; Genetic Markers - genetics; Genetic susceptibility; Glycoproteins; Haplotypes; Health aspects; Histocompatibility antigens; HLA histocompatibility antigens; HLA-A Antigens - genetics; HLA-A Antigens - immunology; Human Genetics; Humans; Immunology; Interdisciplinary aspects; Italy; Linkage Disequilibrium; Multiple sclerosis; Multiple Sclerosis - genetics; Multiple Sclerosis - immunology; Myelin Proteins; Myelin-Associated Glycoprotein - genetics; Myelin-Associated Glycoprotein - immunology; Myelin-Oligodendrocyte Glycoprotein; Neurology; Odds Ratio; Original; original-article; Population Groups - genetics; Risk Factors; Italy; genetic association; HLA-class I markers; multiple sclerosis; Myelin Oligodendrocyte Glycoprotein; extended HLA haplotypes
• ISSN: 1466-4879; 1476-5470
• DOI: 10.1038/gene.2009.101

Previous studies reported an association with multiple sclerosis (MS) of distinct HLA-class I markers, namely
HLA-A*02
,
HLA-Cw*05
and
MOG-142L
. In this work, we tested the association with MS of
A*02
and
Cw*05
in 1273 Italian MS patients and 1075 matched controls, which were previously analyzed for
MOG-142
, and explored the relationship among these three markers in modulating MS risk.
HLA-A*02
conferred a statistically robust MS protection (odds ratio, OR=0.61; 95% confidence intervals, CI=0.51–0.72,
P
<10
−9
), which was independent of
DRB1*15
and of any other
DRB1*
allele and remained similar after accounting for the other two analyzed class I markers. Conversely, the protective effect we previously observed for
MOG-142L
was secondary to its linkage disequilibrium with
A*02
.
Cw*05
was not associated considering the whole sample, but its presence significantly enhanced the protection in the
HLA-A*02-
positive group, independently of
DRB1
: the OR conferred by
A*02
in
Cw*05-
positive individuals (0.22, 95% CI=0.13–0.38) was significantly lower than in
Cw*05-
negative individuals (0.69, 95% CI=0.58–0.83) with a significant (
P
=4.94 × 10
−5
) multiplicative interaction between the two markers. In the absence of
A*02
,
Cw*05
behaved as a risk factor, particularly in combination with
DRB1*03
(OR=3.89,
P
=0.0006), indicating that
Cw*05
might be a marker of protective or risk haplotypes, respectively.