Investigation of gene–gene interactions between CD40 and CD40L in Polish multiple sclerosis patients

Abstract CD40–CD40L interaction is necessary for the activation of both humoral and cellular immune response and has been suggested to play a role in the pathogenesis of multiple sclerosis (MS). Therefore, we analyzed the combined influence of the CD40 and CD40L variants on MS susceptibility and progression on well-defined Polish population. Our investigation revealed that CT individuals in rs1883832 locus of CD40 possessed almost 1.5-fold higher risk for MS than CC individuals (OR = 1.44; 95%CI = 1.03–2.1; p  = 0.032), while this risk for TT individuals was almost 2.5-fold higher (OR = 2.36; 95%CI = 1.19–4.78; p  = 0.014). Moreover, for the first time, we observed the association of CD40 gene with MS development and progression. We observed that for the rs1883832CC individuals the age at diagnosis was on average 2 years lower than for the rs1883832CT and rs1883832TT individuals (CI95% = −3.69 − (−0.29); p  = 0.023). Additionally, we detected that individuals with TT and CT genotypes showed lower risk of developing secondary progressive course in comparison to those with CC genotype. For rs1883832TT individuals this risk was 4-fold lower (HR = 0.24; CI95% = 0.10–0.53; p  = 0.00062). Despite the fact that CD40–CD40L pathway plays a key role in development of autoimmune diseases, we were not able to detect gene–gene interactions between CD40 and CD40L polymorphisms associated with multiple sclerosis.