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PMID: 19654877 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

Association between protective and deleterious HLA alleles with multiple sclerosis in Central East Sardinia.

PloS one ·Vol. 4 ·No. 8 ·2009-08-05 ·Pages e6526

Pastorino R, Menni C, Barca M, Foco L, Saddi V, Gazzaniga G, Ferrai R, Mascaretti L, Dudbridge F, Berzuini C, Murgia SB, Piras ML, Ticca A, Bitti PP, Bernardinelli L

Abstract

The human leukocyte antigen (HLA) complex on chromosome 6p21 has been unambiguously associated with multiple sclerosis (MS). The complex features of the HLA region, especially its high genic content, extreme polymorphism, and extensive linkage disequilibrium, has prevented to resolve the nature of HLA association in MS. We performed a family based association study on the isolated population of the Nuoro province (Sardinia) to clarify the role of HLA genes in MS. The main stage of our study involved an analysis of the ancestral haplotypes A2Cw7B58DR2DQ1 and A30Cw5B18DR3DQ2. On the basis of a multiplicative model, the effect of the first haplotype is protective with an odds ratio (OR) = 0.27 (95% confidence interval CI 0.13-0.57), while that of the second is deleterious, OR 1.78 (95% CI 1.26-2.50). We found both class I (A, Cw, B) and class II (DR, DQ) loci to have an effect on MS susceptibility, but we saw that they act independently from each other. We also performed an exploratory analysis on a set of 796 SNPs in the same HLA region. Our study supports the claim that Class I and Class II loci act independently on MS susceptibility and this has a biological explanation. Also, the analysis of SNPs suggests that there are other HLA genes involved in MS, but replication is needed. This opens up new perspective on the study of MS.

MeSH Terms
Alleles Genotype HLA Antigens/genetics Haplotypes Humans Italy Multiple Sclerosis/genetics Polymorphism, Single Nucleotide Regression Analysis
Chemicals
HLA Antigens
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Pastorino Roberta
Dipartimento di Scienze Sanitarie Applicate e Psicocomportamentali, Università di Pavia, Pavia, Italy. roberta.pastorino@unipv.it
Menni Cristina
Barca Monserrata
Foco Luisa
Saddi Valeria
Gazzaniga Giovanna
Ferrai Raffaela
Mascaretti Luca
Dudbridge Frank
Berzuini Carlo
Murgia Salvatore Bruno
Piras Maria Luisa
Ticca Anna
Bitti Pier Paolo
Bernardinelli Luisa
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Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
DOI
10.1371/journal.pone.0006526
Email
roberta.pastorino@unipv.it
Published
2009-08-05
Epub
2009-00-05
Pages
e6526
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC2716537
Subset
IM
Grants
Medical Research Council · G0802320 · United Kingdom
Medical Research Council · MC_U105292688 · United Kingdom
External Links
PubMed source DOI: 10.1371/journal.pone.0006526 PMC Full Text View journal details
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