We confirm that: (i) basally there is genotype dependent effect on gene expression in carriers of the susceptible CD28 variant; (ii) an interplay between viral infection and genotype might be also important for CD28 expression; (iii) signaling of CD28 is not different across the genotypes and neither is their response to vitamin D; and (iv) there is a genotype effect on response to TNFα inflammatory stimuli, which can be overcome by vitamin D. This evidence concerns the gene CD28 and viral infectious disease.