title: Association between protective and deleterious HLA alleles with multiple sclerosis in Central East Sardinia.
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.
authors: Dipartimento di Scienze Sanitarie Applicate e Psicocomportamentali, Università di Pavia, Pavia, Italy. roberta.pastorino@unipv.it
authors: Roberta
authors: R
authors: Pastorino
authors: Cristina
authors: C
authors: Menni
authors: Monserrata
authors: M
authors: Barca
authors: Luisa
authors: L
authors: Foco
authors: Valeria
authors: V
authors: Saddi
authors: Giovanna
authors: G
authors: Gazzaniga
authors: Raffaela
authors: R
authors: Ferrai
authors: Luca
authors: L
authors: Mascaretti
authors: Frank
authors: F
authors: Dudbridge
authors: Carlo
authors: C
authors: Berzuini
authors: Salvatore Bruno
authors: SB
authors: Murgia
authors: Maria Luisa
authors: ML
authors: Piras
authors: Anna
authors: A
authors: Ticca
authors: Pier Paolo
authors: PP
authors: Bitti
authors: Luisa
authors: L
authors: Bernardinelli
mesh_terms: D000483:Alleles; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007558:Italy; D009103:Multiple Sclerosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis
chemical_list: D006680:HLA Antigens