1. Association between protective and deleterious HLA alleles with multiple sclerosis in Central East Sardinia
- Author
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Raffaela Ferrai, Roberta Pastorino, Valeria Saddi, L. Mascaretti, Giovanna Gazzaniga, Luisa Foco, Salvatore Bruno Murgia, Monserrata Barca, Frank Dudbridge, Pier Paolo Bitti, Luisa Bernardinelli, Maria Luisa Piras, Cristina Menni, Anna Ticca, Carlo Berzuini, Pastorino, R, Menni, C, Barca, M, Foco, L, Saddi, V, Gazzaniga, G, Ferrai, R, Mascaretti, L, Dudbridge, F, Berzuini, C, Murgia, S, Piras, M, Ticca, A, Bitti, P, and Bernardinelli, L
- Subjects
Linkage disequilibrium ,Multiple Sclerosis ,Genotype ,MED/03 - GENETICA MEDICA ,lcsh:Medicine ,Immunology/Autoimmunity ,Single-nucleotide polymorphism ,Neurological Disorders/Multiple Sclerosis and Related Disorders ,Human leukocyte antigen ,Genetics and Genomics/Complex Traits ,Major histocompatibility complex ,Polymorphism, Single Nucleotide ,multiple sclerosis, HLA, ancestral haplotypes, isolated population ,Polymorphism (computer science) ,HLA Antigens ,Humans ,Allele ,lcsh:Science ,Alleles ,Genetics ,Multidisciplinary ,biology ,Haplotype ,lcsh:R ,Haplotypes ,Italy ,biology.protein ,Regression Analysis ,lcsh:Q ,Genetics and Genomics/Genetics of the Immune System ,Research Article - 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.
- Published
- 2009