Background. SNP rs9275596, situated between HLA-DQB1 and HLA-DQA2, is linked to MS risk in Latvians. Its effect on disease-modifying therapy (DMT) outcomes is unexplored.
Aim. Assess the impact of rs9275596 on two-year clinical response to DMTs.
Methods. Among 296 registry patients, 230 received 342 treatment courses. Annual change in Expanded Disability Status Scale (ΔEDSS) and “no evidence of disease activity” (NEDA) status were analysed by genotype (α = 0.05).
Results and Discussion. In patients on less frequently used therapies (e.g., mitoxantrone, azathioprine), rare-allele homozygotes TT showed an average first-year ΔEDSS of –0.30 ± 0.75, which was significantly better than common homozygotes CC (0.20 ± 0.26; p = 0.038), suggesting a protective TT effect with these drugs.
In contrast, patients carrying the TT genotype who were treated with glatiramer acetate (GA) had worse outcomes, showing an average EDSS increase of 0.41 ± 0.80 during the first year, which was significantly higher than those receiving other treatments (p = 0.024; η = 0.36). This indicates a genotype-specific adverse response to GA. No significant differences between genotypes were observed in the second year of therapy or in NEDA status, suggesting that the influence of rs9275596 is limited to early treatment response and may depend on the specific therapy used.
Conclusions. The HLA variant rs9275596 appears to influence short-term treatment response in Latvian MS patients. TT genotype carriers show better outcomes with less commonly used therapies but respond poorly to glatiramer acetate (GA), while CC carriers tend to benefit more from GA. These findings suggest that rs9275596 may serve as a pharmacogenetic marker to guide therapy selection, warranting further validation.
Funding. UL 1.1.1.2/VIAA/4/20/718; ERDF 1.1.1.1/16/A/016; UL Foundation (MikroTik) 40021.