Exploring the association between STAT4 rs7601754 polymorphism and vision impairment in multiple sclerosis

Background. Multiple sclerosis (MS) is an autoimmune disorder that affects the central nervous system and is characterised by gliosis, demyelination, inflammation, and degeneration of nerve cells [1]. Young adults with MS, usually between the ages of 20 and 30, often present with unilateral optic neuritis, partial myelitis, sensory abnormalities, or brainstem syndromes [2]. MS and Signal Transducer and Activator of Transcription 4 (STAT4) may be interconnected, as MS has been associated with immune system dysfunction [3]. Janus kinases (JAKs) are the proteins that enable members of class I and class II cytokine receptor families to transmit their signals. Once activated, JAKs phosphorylate the STATs. After phosphorylation, the STAT proteins undergo cytoplasmic dimerization before translocating to the nucleus, where they bind to deoxyribonucleic acid (DNA) regulatory elements and initiate gene transcription. Consequently, variations in STAT4 expression or activity may influence the immune system’s normal response and function, potentially resulting in immunosuppression or autoimmune disorders [4]. Overall, the connection between the STAT4 gene and MS suggests that dysregulation of the immune system plays a significant role in the development of the disease [3]. Aim. This study aimed to evaluate the association between the STAT4 rs7601754 polymorphism and vision impairment in individuals with MS. Methods. Altogether, 400 patients were enrolled in the study (MS patients with vision impairment (n = 131), MS patients without vision impairment (n = 69), and healthy controls as a reference group (n = 200)). Blood samples were collected, and the DNA salting-out method was used for DNA extraction from peripheral venous blood. Genotyping of STAT4 rs7601754 was performed using RT-PCR. Results. We found that the STAT4 rs7601754 A allele was statistically significantly less frequent in MS patients with and without vision impairment compared to the reference group (p = 0.046, p < 0.001, respectively). Binary logistic regression analysis revealed that the AG + GG genotypes are associated with 2.7-fold increased odds of not having visual impairment in MS patients (OR: 2.656; CI: 1.493–4.724; p < 0.001). Conclusion. This study aimed to enhance the understanding of its role in the development of vision-related symptoms in MS patients, potentially revealing a biomarker for vision impairment in MS. STAT4 rs7601754 AG + GG genotypes are linked to a 2.7-fold increase in the odds of not experiencing visual impairment in MS patients.