Association between the IL2RA polymorphism and type 1 diabetes risk: Family based association study

As part of an ongoing search for genes associated with type 1 diabetes (T1D), a common autoimmune disease, we tested the candidate genes; IL2RA (CD25), which encodes a subunit (IL2Rα) of the high-affinity interleukin-2 (IL2) receptor complex and IL2RB, encodes a subunit (IL-2Rβ). In order to underline the role of these genes involved in control of T-cell immune responses and autoimmunity, we investigated, using the Sequenom MassARRAY platform, thirty five variants from two genes: 25 SNPs from IL2RA gene and ten SNPs from IL2RB gene in 59 T1D Tunisian families.Using the Family-based association test (FBAT), which uses generalized score statistics to perform a variety of transmission disequilibrium tests (TDT), we performed a statistical analysis under the default model (additive) in order to evaluate allelic and genotypic transmission from parent to affect offspring. We observed an overtransmission of alleles from parents to affected child at tow variants of IL2RA: (rs2104286, allele T, P = 0.027; z = 2.209; rs791589, allele G, P = 0.043; z = 2.021). When haplotypes were constructed, we also identified an overtransmission of TTCCA haplotype (P = 0.017) derived from the haplotype analysis across the five IL2RA markers (rs706778 rs2104286/rs7072793/rs7073236/rs11597367), while CCTTA haplotype was undertransmitted to affect children (P = 0.0124).These findings confirm the role of IL2RA involved in the T cell regulation pathway in the development of T1D in Tunisian families. The association of IL2RA/CD25 with a fifth autoimmune disease suggests that this gene appears to play a vital role in immune regulation and function as well as predisposition to autoimmunity in general. Further investigation of the gene using both genetic and functional approaches is required.