FCRL3 −169CT functional polymorphism in type 1 diabetes and autoimmunity traits

A functional variant located in the promoter region of the Fc receptor like 3 gene (FCRL3, −169CT variant) has been recently shown to be associated with several autoimmune diseases in the Japanese population. Following the concept of shared genetic determinants between autoimmune diseases, we tested this variant for association to Type 1 diabetes (T1D) and T1D-related phenotypes in two independent settings: a family-based association study (French and US families) and a case-control study (French population). We found suggestive evidence for association of the FCRL3 −169CC genotype, corresponding to the susceptibility genotype for rheumatoid arthritis, with an increased risk of additional autoimmunity markers (OR = 1.97, P = 0.01) and of other autoimmune diseases (OR = 1.75, P = 0.05). However, there was no evidence of association of this variant with T1D in these cohorts, separately and combined, nor in subgroups of patients defined based on their major T1D risk factors at HLA-DRB1, insulin and PTPN22. Hence, this variant may help define subgroups of T1D patients with contrasted risk of other autoimmune diseases.