Journal
GENES AND IMMUNITY
Volume 11, Issue 2, Pages 173-180Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/gene.2009.101
Keywords
multiple sclerosis; HLA-class I markers; extended HLA haplotypes; Myelin Oligodendrocyte Glycoprotein; genetic association
Categories
Funding
- Italian Foundation for Multiple Sclerosis [2001/R/44, 2002/R/40, 2005/R/10, 2008/R/11]
- CARIPLO Foundation, Regione Piemonte Ricerca Sanitaria Finalizzata [2003, 2004, 2007, 2008]
- Regione Piemonte CIPE
- Ministry of Health [2004.80]
- Eastern Piedmont University
- Compagnia di San Paolo (Turin)
- Fondazione CRT (Turin)
- Fondazione Monzino
- Ospedale Maggiore Policlinico and Ing. Cesare Cusan
- FISM [2003/B/2]
- PhD Lagrange Fellowship
Ask authors/readers for more resources
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. Genes and Immunity (2010) 11, 173-180; doi: 10.1038/gene.2009.101; published online 12 November 2009
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available