PMID- 19654877
OWN - NLM
STAT- MEDLINE
DCOM- 20100119
LR  - 20211020
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 4
IP  - 8
DP  - 2009 Aug 5
TI  - Association between protective and deleterious HLA alleles with multiple 
      sclerosis in Central East Sardinia.
PG  - e6526
LID - 10.1371/journal.pone.0006526 [doi]
LID - e6526
AB  - 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.
FAU - Pastorino, Roberta
AU  - Pastorino R
AD  - Dipartimento di Scienze Sanitarie Applicate e Psicocomportamentali, Universita di 
      Pavia, Pavia, Italy. roberta.pastorino@unipv.it
FAU - Menni, Cristina
AU  - Menni C
FAU - Barca, Monserrata
AU  - Barca M
FAU - Foco, Luisa
AU  - Foco L
FAU - Saddi, Valeria
AU  - Saddi V
FAU - Gazzaniga, Giovanna
AU  - Gazzaniga G
FAU - Ferrai, Raffaela
AU  - Ferrai R
FAU - Mascaretti, Luca
AU  - Mascaretti L
FAU - Dudbridge, Frank
AU  - Dudbridge F
FAU - Berzuini, Carlo
AU  - Berzuini C
FAU - Murgia, Salvatore Bruno
AU  - Murgia SB
FAU - Piras, Maria Luisa
AU  - Piras ML
FAU - Ticca, Anna
AU  - Ticca A
FAU - Bitti, Pier Paolo
AU  - Bitti PP
FAU - Bernardinelli, Luisa
AU  - Bernardinelli L
LA  - eng
GR  - G0802320/MRC_/Medical Research Council/United Kingdom
GR  - MC_U105292688/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090805
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (HLA Antigens)
SB  - IM
MH  - *Alleles
MH  - Genotype
MH  - HLA Antigens/*genetics
MH  - Haplotypes
MH  - Humans
MH  - Italy
MH  - Multiple Sclerosis/*genetics
MH  - Polymorphism, Single Nucleotide
MH  - Regression Analysis
PMC - PMC2716537
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2009/08/06 09:00
MHDA- 2010/01/20 06:00
PMCR- 2009/08/05
CRDT- 2009/08/06 09:00
PHST- 2008/11/20 00:00 [received]
PHST- 2009/07/05 00:00 [accepted]
PHST- 2009/08/06 09:00 [entrez]
PHST- 2009/08/06 09:00 [pubmed]
PHST- 2010/01/20 06:00 [medline]
PHST- 2009/08/05 00:00 [pmc-release]
AID - 08-PONE-RA-07423R2 [pii]
AID - 10.1371/journal.pone.0006526 [doi]
PST - epublish
SO  - PLoS One. 2009 Aug 5;4(8):e6526. doi: 10.1371/journal.pone.0006526.