A single nucleotide polymorphism in the CD40 gene on chromosome 20q (GD-2) provides no evidence for susceptibility to Graves' disease in UK Caucasians.

A genome-wide screen in Graves' disease (GD) has shown linkage to chromosome 20q, designated GD-2. The gene encoding CD40, which stimulates lymphocyte proliferation and differentiation, maps to this region, and a single nucleotide polymorphism (SNP) at position -1 of the Kozak sequence within the gene has been reported to be associated with GD. The aim of this study was to determine whether this SNP of the CD40 gene confers susceptibility to GD in UK Caucasians. A large case-control cohort consisting of 800 patients with GD, and 785 control subjects with no history of autoimmune disease, was used to genotype this SNP by polymerase chain reaction restriction fragment length polymorphism. Despite adequate power (> 99%) to detect an effect, if present (odds ratio of 1.5), no significant difference in allele or genotype frequency of the CD40 SNP was observed between patients with GD and control subjects (P = 0.087 and P = 0.145, respectively). These data suggest that this polymorphism of the CD40 gene is not associated with GD in the UK and is therefore not contributing to disease susceptibility in the chromosomal region designated GD-2.