Multiple sclerosis (MS) is among the most common autoimmune disorders and is characterized by inflammation and degeneration affecting the central nervous system. Glatiramer acetate (GA) is an immunomodulatory drug utilized for treating relapsing-remitting MS. However, a considerable number of patients do not exhibit an appropriate response to this drug. This condition is known as GA resistance. This study aimed to investigate the relationship between nucleotide variations in the HLA-DRA, HLA-DQA1 and IL-6 genes and GA resistance. Additionally, the relationship of environmental factors with MS was investigated. One hundred thirty-nine MS patients were enrolled in this study. Patients were divided into two groups: non-responders (n = 58) and responders (n = 81). After DNA was isolated from peripheral blood, the rs3135388 and rs3135391 variations in HLA-DRA, the rs9272346 variation in HLA-DQA1, and the rs1800795 and rs1900796 variations in IL-6 were analyzed by Real-Time Polymerase Chain Reaction (RT-PCR). At the end of the study, it was found that the number of females was approximately 3 times greater in responders and 4 times greater in non-responders than in males. When nucleotide variations and allele distributions were compared between the groups, no significant relationships were found. Similarly, no significant relationship was found between risk factors and nucleotide variations. However, in non-responders, the expanded disability status scale and lesion load were found to be significantly high. In conclusion, by increasing the number of patients, more meaningful results can be achieved in future studies. Elucidating the pharmacogenetic characteristics (the drug-gene relationship) of MS patients using GA could lead to the development of personalized treatment strategies.

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http://dx.doi.org/10.1007/s10528-025-11077-4DOI Listing

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