HLA-class I markers and multiple sclerosis susceptibility in the Italian population.
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 x 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.
Bergamaschi
L
L
Department of Medical Sciences and Interdisciplinary Research Center of Autoimmune Diseases, University of Eastern Piedmont, Via Solaroli 17, Novara, Italy.
Leone
M A
MA
Fasano
M E
ME
Guerini
F R
FR
Ferrante
D
D
Bolognesi
E
E
Barizzone
N
N
Corrado
L
L
Naldi
P
P
Agliardi
C
C
Dametto
E
E
Salvetti
M
M
Visconti
A
A
Galimberti
D
D
Scarpini
E
E
Vercellino
M
M
Bergamaschi
R
R
Monaco
F
F
Caputo
D
D
Momigliano-Richiardi
P
P
D'Alfonso
S
S
D000483:Alleles; D004198:Disease Susceptibility / Q000276:immunology*; D005819:Genetic Markers / Q000235:genetics*; D015234:HLA-A Antigens / Q000235:genetics* / Q000276:immunology; D006239:Haplotypes; D006801:Humans; D007558:Italy; D015810:Linkage Disequilibrium; D009103:Multiple Sclerosis / Q000235:genetics* / Q000276:immunology; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000235:genetics / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D016017:Odds Ratio; D044382:Population Groups / Q000235:genetics*; D012307:Risk Factors
D005819:Genetic Markers; D015234:HLA-A Antigens; C571326:MOG protein, human; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein