Optic neuritis: exploring genetic associations of EXOC3L1 and TNF in the Lithuanian population

Optic neuritis (ON) is a common cause of acute optic nerve damage in adults [1]. It is characterized by optic nerve inflammation, demyelination and secondary axonal damage, leading to retinal ganglion cell (RGC) apoptosis [2]. ON typically manifests around the age of 36 and is classified as either typical or atypical [3]. Typical ON is often associated with optic nerve demyelination and may occur in isolation or as part of multiple sclerosis (MS). In contrast, atypical ON is linked to infections, autoimmune disorders, or neuromyelitis optica spectrum disorders (NMOSD) [4]. Tumor Necrosis Factor (TNF) is a key pro-inflammatory cytokine involved in immune system regulation and various pathological conditions, including inflammation and tumorigenesis [5,6]. Single nucleotide polymorphisms (SNPs) in the TNF-α promoter region are associated with susceptibility to infectious and inflammatory diseases [7]. The EXOC3L1 gene is implicated in insulin secretion, protein exocytosis following brain injury, spontaneous apoptosis induction, and high-density lipoprotein regulation. However, it is precise biological functions remain unclear [8]. In this study we investigated the associations between TNF, EXOC3L1 gene polymorphisms and the occurrence of ON. A total of 82 patients with ON and 160 healthy controls were included in the study. DNA was extracted from peripheral blood leukocytes using the DNA salting-out method. Genotyping was performed using the real-time polymerase chain reaction (RT-PCR) method. Statistical data analysis was performed with ”IBM SPSS Statistics 29.0”. Our analysis revealed statistically significant differences in the distribution of genotypes and alleles for EXOC3L1 rs868213. The EXOC3L1 rs868213 G allele was significantly less frequent in patients with ON compared to the control group (1.2% vs. 5.6%, respectively, p = 0.021). In contrast, statistical analysis of TNF rs2229094 showed no significant differences. Binary logistic regression also showed no significant differences. Our study identifies an association between EXOC3L1 rs868213 and the occurrence of optic neuritis in the Lithuanian population.