Biochemical and Genetic Association of Plasma Vitamin D Levels and Vitamin D Receptor Gene Polymorphisms with Primary Sjögren’s Syndrome in the Tunisian Population

Sjögren’s syndrome is a chronic autoimmune disorder characterized by dysfunction of exocrine glands, primarily manifesting as xerostomia and keratoconjunctivitis sicca. Although its pathogenesis remains incompletely elucidated, microRNAs (miRNAs) have been increasingly recognized as potential regulators of immune homeostasis. These small non-coding RNAs exert epigenetic control by modulating gene expression post-transcriptionally, primarily through mRNA degradation or translational repression, thereby influencing key inflammatory and immunological pathways. In this case-control study, we investigated the association of three miRNA gene polymorphisms (rs2910164 in miR-146a, rs11614913 in miR-196a2, and rs3746444 in miR-499) with susceptibility to Sjögren’s syndrome in a Tunisian cohort. A total of 120 patients diagnosed with Primary Sjögren’s syndrome and 147 age- and sex-matched healthy controls were genotyped using the polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) method. Statistical analysis revealed a significant association between the miR-499 rs3746444 polymorphism and increased disease risk, with the GG genotype conferring the highest susceptibility (odds ratio [OR] = 9.4, p < 0.001). Conversely, the T allele of the miR-196a2 rs11614913 variant exhibited a protective effect (OR = 0.62, p = 0.018). No statistically significant association was observed for miR-146a rs2910164. These findings underscore the potential involvement of miRNA-related genetic variants in the etiology of Sjögren’s syndrome and highlight the importance of population-specific genetic studies in autoimmune pathogenesis.