Expression of genes involved in susceptibility to multifactorial autoimmune diseases: estimating genotype effects.

Several single nucleotide polymorphisms (SNPs) have been associated with susceptibility to autoimmune diseases, but the mechanisms responsible for the associations are poorly understood. To test the hypothesis that the variation of the basal levels of the gene products is significantly influenced by genetic polymorphism, we investigated whether SNPs in genes CD40, CD28, CTLA4, CD80, CD86, BAFF and IL6 are affecting mRNA or protein expression. The surface expression of the proteins on unstimulated monocytes, B cells, NK cells, CD4+ T cells and CD8+ T cells, as well as the mRNA levels in peripheral blood mononuclear cells (PBMC) was compared among healthy volunteers with different genotypes. Despite the low basal expression level and large interindividual variation, average BAFF expression was significantly higher in carriers of genotype C/C of the BAFF-871C>T SNP (rs9514828) when compared with carriers of the C/T and T/T genotypes. Genotype C/C carriers presented higher levels of the protein on CD8+ T cells, monocytes and NK cells and of mRNA in PBMC. Moreover, carriers of T allele of CTLA4-318C>T (rs5742909) showed a significantly increased expression of CTLA-4 on CD8+ T cells. No significant variation among genotypes was found in the protein or mRNA levels of other investigated genes.