HLA class II alleles in patients with multiple sclerosis in the Biscay province (Basque Country, Spain).

Genetic susceptibility to multiple sclerosis (MS) is associated with genes of the major histocompatibility complex, particularly with the HLA DRB11501-DQA10102-DQB10602 haplotype in Caucasians. To investigate the association of DRB1, DQA1 and DQB1 alleles and haplotypes with MS in Biscay, Basque Country, northern Spain, we examined 197 patients and 200 regionally matched controls. High resolution HLA class II typing was performed by polymerase chain reaction followed by sequence-specific oligonucleotide probe hybridization. Several alleles were overrepresented in MS patients compared with those of controls: DRB10402, DRB11303, DRB11501, DQA10102, DQB10301, and DQB10602. DQB10602 was the only potentially predisposing allele for MS that withstood Bonferroni correction and maintained the association in a logistic regression model. On the other hand, several alleles showed lower frequencies in the MS group: DRB10101, DQA10101, DQB10303, and DQB10501, but only DRB10101 and DQB10303 maintained a negative association with the disease in the regression analysis. Three haplotypes were identified as potentially predisposing for MS in our population: DRB11501-DQA10102-DQB10602, DRB10402-DQA10301-DQB10302, and HLA-DRB1013-DQA105-DQB10301. Additionally, three haplotypes associated with a lower risk for MS were identified, exhibiting DRB10101-DQA10101-DQB10501 the strongest negative association with MS [12% in controls vs. 3.8% in MS, Pc = 0.00047, OR = 0.290 (95% CI = 0.160–0.528)], and suggesting, therefore, a putative protective role for this haplotype in the population under study.