OAS1: a multiple sclerosis susceptibility gene that influences disease severity

Area of Science:

• Immunogenetics
• Neuroimmunology

Background:

• Type 1 interferons modulate oligoadenylate synthetase 1 (OAS1) expression.
• A single nucleotide polymorphism (SNP) in OAS1 exon 7 influences RNAseL enzyme activity.
• The OAS1 A allele results in a truncated, low-activity enzyme, while the G allele yields a high-activity enzyme.

Purpose of the Study:

• To investigate the association between OAS1 genotypes and multiple sclerosis (MS) susceptibility.
• To determine if OAS1 genotypes correlate with disease activity in patients with relapsing-remitting MS (RRMS).

Main Methods:

• Genotype distribution of OAS1 was analyzed in 401 MS patients and 394 healthy controls.
• OAS1 genotypes were assessed in 178 RRMS patients treated with interferon-beta (IFNbeta), categorized by disease activity.
• A subgroup of 65 RRMS patients with highly active disease was specifically examined.

Main Results:

• OAS1 genotype distribution significantly differed between MS patients and controls (p=0.000003), with fewer GG homozygotes in MS patients.
• The AA genotype was more prevalent in MS patients with disease activity despite IFNbeta (51%) compared to those with minimal activity (32%).
• Patients with the AA genotype had a shorter median time to first relapse on IFNbeta (24 months) than those with AG or GG genotypes (33 months).

Conclusions:

• The OAS1 AA genotype is associated with increased susceptibility to MS.
• The OAS1 GG genotype appears to be protective against increased disease activity in MS patients treated with IFNbeta.