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

Area of Science:

• Immunogenetics
• Neuroimmunology
• Human Genetics

Background:

• Multiple sclerosis (MS) genetic risk in Northern Europeans is linked to human leucocyte antigen (HLA) genes.
• Ireland exhibits an MS prevalence gradient, with higher rates in the north (Donegal) and lower rates in the southeast (Wexford).

Purpose of the Study:

• To investigate heterogeneity in HLA class II associations with MS within Ireland.
• To identify specific HLA-DRB1 and -DQB1 haplotypes predisposing or protecting against MS in Irish populations.
• To evaluate the association of HLA-DRB1 and -DQB1 haplotypes with MS in Wexford and Donegal.

Main Methods:

• Genotyping of HLA-DRB1 and -DQB1 alleles in 118 MS patients and 400 controls from Wexford and Donegal.
• Statistical analysis to determine haplotype associations and frequencies.
• Comparison of haplotype carriage and homozygosity rates between high-risk (Donegal) and low-risk (Wexford) areas.

Main Results:

• The HLA-DRB1*1501-DQB1*0602 haplotype was significantly associated with MS in both Wexford (OR=2.95) and Donegal (OR=2.29).
• Higher frequency and homozygosity rates of the DRB1*1501-DQB1*0602 haplotype were observed in Donegal compared to Wexford.
• Evidence of heterogeneity in HLA class II associations with MS within Ireland was established.

Conclusions:

• The DRB1*1501-DQB1*0602 haplotype is a significant genetic risk factor for MS in Ireland.
• Differences in the frequency and homozygosity of this haplotype likely contribute to the observed MS prevalence gradient.
• HLA class II associations with MS display significant heterogeneity across different regions of Ireland.