CXCL8 rs2227306 and Its Role in Relapsing-Remitting Multiple Sclerosis

Introduction Multiple sclerosis (MS) is an inflammatory autoimmune disease that causes neurological impairment in young individuals by damaging neurons in the central nervous system (CNS) (1). Relapsing-remitting MS (RRMS) affects 80% of individuals with the disease. MS is a complex disorder, with both genetic and environmental factors contributing to its onset and progression, even though its exact etiology and pathophysiology remain unknown (2). Multiple genes contribute to the development of MS, and gene-environment interactions are also crucial for the onset of the disease. The International MS Genetics Consortium has linked more than 200 genetic variations to an increased risk of disease. Many of these variations are found in genes related to vitamin D production, immune modulation, and maintaining the integrity of the myelin sheath (3). Innate immunity involves the proinflammatory chemokine CXCL8 (4). CXCL8 is one of the cytokines released by activated astrocytes. By inducing inflammatory processes that hinder oligodendrocytes from surviving and forming myelin, CXCL8 can lead to neuronal injury. Aim To determine CXCL8 rs2227306 in RRMS patients and healthy controls, and relate the obtained results to RRMS occurrence and brain stem and cerebellum damages. Methods 500 patients were enrolled in the study (250 patients with RRMS and 250 healthy controls as a reference group). The 2017 McDonald diagnostic criteria, which included positive oligoclonal bands, typical demyelinating lesions found in brain/spinal cord MRI scans (per the MAGNIMS criteria), and clinical symptoms/relapse, have been used to establish the diagnosis of MS in patients. Blood samples were collected, and the DNA salting-out method was used for DNA extraction from peripheral venous blood. Genotyping of CXCL8 rs2227306 was performed using real-time polymerase chain reaction. Results Our study showed that the CXCL8 rs2227306 CC genotype was statistically significantly more frequent in RRMS patients compared with the control group (35.6 vs. 26.4; p = 0.026). Binary logistic regression analysis revealed that CXCL8 rs2227306 was statistically significantly associated with a 1.5-fold decreased odds of RRMS under the dominant model (OR =0.649; 95% CI: 0.443-0.951; p = 0.027). We investigated the associations between the occurrence of genotypes and lesions in the brain stem and cerebellum. Binary logistic regression analysis revealed that CXCL8 rs2227306 was statistically significantly associated with a 2-fold decreased odds in RRMS patients without cerebellum impairment (OR:0.506; CI: 0.321-0.799; p = 0.003). Moreover, binary logistic regression analysis revealed that the CT+TT genotypes are associated with 1.9-fold decreased odds of RRMS occurrence without brain stem impairment (OR:0.538; CI: 0.337-0.858; p = 0.009). Conclusions The CXCL8 rs2227306 was associated with RRMS occurrence and decreased the odds of RRMS without brain stem and cerebellum impairments. These findings highlight a potential genetic marker for RRMS that may help refine patient stratification and disease monitoring.