Human leucocyte antigen class II polymorphism in Irish patients with multiple sclerosis

The contribution of human leucocyte antigen (HLA) to the genetic risk for multiple sclerosis (MS) in patients of Northern European Caucasoid ancestry has been known since the 1970s. The northern part of Ireland, including county Donegal, is known to be a high-risk area for the development of MS. Recorded prevalence rates for county Wexford in the south-east Ireland have been markedly lower and suggest the existence of a prevalence gradient within the island. To evaluate the association of HLA-DRB1 and -DQB1 haplotypes with MS in both Wexford and Donegal, we examined a total of 118 patients and 400 regionally matched controls. The aim of this exploratory study was to test the possibility of heterogeneity in HLA class II associations with MS and to identify potential predisposing or protective haplotypes, associated with MS risk in Ireland. We confirmed the association of DRB1*1501-DQB1*0602 haplotype carriage with MS in both Wexford [odds ratio (OR) = 2.95, P = 0.0020, P-cor = 0.0220] and Donegal (OR = 2.29, P = 0.0030, P-cor = 0.0420). A higher frequency and a significantly higher homozygosity rate of this haplotype in Donegal are likely contributing factors to the higher prevalence of MS in Donegal compared with Wexford. The distribution of HLA class II alleles among Irish MS patients and controls establishes that there is heterogeneity in HLA class II associations with MS within Ireland.